Biomedical subjects

B S Huang

Publications and source records attributed to B S Huang.

At least 19 recordsLinked to original sources

PubMed2001

Central sympathoinhibitory effects of calcium channel blockers.

It is generally assumed that the arterial vasodilation induced by inhibition of Ca(2+) influx into vascular smooth muscle cells represents the main mechanism for the hypotensive effect of dihydropyridine calcium channel blockers. Increases in sympathetic tone have been related to activation of the arterial baroreflex by rapid lowering of blood pressure. This review highlights new findings in two areas. First, in animal studies, direct central administration of dihydropyridines such as nifedipine or amlodipine lowers sympathetic nerve activity and thereby blood pressure. Peripheral administration of nifedipine or amlodipine at low rates appears to result in gradual accumulation of drug in the central nervous system, and also causes lowering of sympathetic nerve activity and thereby lowering of blood pressure (rather than by arterial vasodilation). Second, in hypertensive humans treated with long-acting dihydropyridines and presumably little activation of the arterial baroreflex, some studies have demonstrated lowering of sympathetic activity (as assessed by plasma norepinephrine), but others reported increases (as assessed by plasma norepinephrine or microneurography). This sympathoexcitatory response may be due to activation of the renin-angiotensin system, particularly at higher doses.

Animals↗

PubMed2001

High salt intake and the brain renin--angiotensin system in Dahl salt-sensitive rats.

OBJECTIVES: To assess changes in the activity of the brain renin-angiotensin system during (i) the development of salt-sensitive hypertension; and (ii) the prevention of salt-sensitive hypertension by blocking brain 'ouabain'. METHODS: In protocol I, angiotensin converting enzyme (ACE) mRNA and activity and angiotensin I and II levels were assessed in the hypothalamus and pons of Dahl salt-sensitive (Dahl S) and salt-resistant (Dahl R) rats on regular (120 micromol Na+ per g) or high (1370 micromol Na+ per g) salt diet from 4-6 weeks or 4-9 weeks of age. In protocol II, ACE mRNA and activity were assessed in the hypothalamus and pons in Dahl S on regular or high salt treated with intracerebroventricular (i.c.v.) Fab fragments blocking brain 'ouabain' or gamma-globulins, and in Dahl R on high or regular salt ACE mRNA was assessed by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) assay and angiotensin I and II by radioimmunoassay after high-performance liquid chromatography. In protocol III, effects of i.c.v. angiotensin I and i.c.v. bradykinin on renal sympathetic nerve activity (RSNA), heart rate and blood pressure before and after i.c.v. captopril were assessed in Dahl S and R rats on regular or high salt intake from 4-8 weeks of age. RESULTS: High salt diet caused a gradual, but marked increase in blood pressure in Dahl S but not Dahl R rats. Dahl S rats showed small but significant increases in ACE mRNA in the hypothalamus on regular salt diet. In Dahl S rats on high salt diet for 2 or 5 weeks ACE mRNA levels significantly increased in both hypothalamus and pons, compared with Dahl R rats on either diet or Dahl S rats on regular diet. After 5 weeks of high salt diet, ACE mRNA levels in the hypothalamus in Dahl S rats were almost three-fold higher and in the pons two-fold higher than in Dahl R rats on either diet or Dahl S on regular salt diet. High salt diet also increased ACE activity of the hypothalamus and pons in Dahl S but not Dahl R. Consistent with this increased ACE activity, central responses to angiotensin I were clearly enhanced and to bradykinin markedly diminished in Dahl S on high salt intake. Chronic blockade of brain 'ouabain' by i.c.v. Fab fragments prevented the increases in blood pressure, ACE mRNA and activity in the hypothalamus and pons by high salt intake in Dahl S rats. Angiotensin I levels in the hypothalamus and pons were similar in both groups of rats and there were no significant changes caused by high salt diet in Dahl S and R rats. On regular salt intake angiotensin II levels in the hypothalamus of Dahl S rats showed a significant decrease as compared with Dahl R rats on regular salt diet, and were similar in the pons of the two strains. High salt intake did not affect angiotensin II levels in either hypothalamus or pons in Dahl S and R rats. CONCLUSIONS: These results indicate that high salt intake increases blood pressure, ACE expression and activity in the hypothalamus and pons of Dahl S rats without a parallel increase in angiotensin II levels. Effects of high salt intake on ACE mRNA and activity appear to be secondary to activation of brain 'ouabain'.

Angiotensin I↗

PubMed2001

Enhanced sympathoexcitatory and pressor responses to central Na+ in Dahl salt-sensitive vs. -resistant rats.

An enhanced responsiveness to increases in cerebrospinal fluid (CSF) Na+ by high salt intake may contribute to salt-sensitive hypertension in Dahl salt-sensitive (S) rats. To test this hypothesis, sympathetic and pressor responses to acute and chronic increases in CSF Na+ were evaluated. In conscious young (5-6 wk old) and adult (10-11 wk old) Dahl S and salt-resistant (R) rats as well as weight-matched Wistar rats, hemodynamic [blood pressure (BP) and heart rate (HR)] and sympathetic [renal sympathetic nerve activity (RSNA)] responses to 10-min intracerebroventricular infusions of artificial CSF (aCSF) and Na+-rich aCSF (containing 0.2-0.45 M Na+) were evaluated. Intracerebroventricular Na+-rich aCSF increased BP, RSNA, and HR in a dose-related manner. The extent of these increases was significantly larger in Dahl S versus Dahl R or Wistar rats and young versus adult Dahl S rats. In a second set of experiments, young Dahl S and R rats received a chronic intracerebroventricular infusion of aCSF or Na+-rich (0.8 M) aCSF (5 microl/h) for 14 days, with the use of osmotic minipumps. On day 14 in conscious rats, CSF was sampled and BP, HR, and RSNA were recorded at rest and in response to air stress, intracerebroventricular alpha2-adrenoceptor agonist guanabenz, intracerebroventricular ouabain, and intravenous phenylephrine and nitroprusside to estimate baroreflex function. The infusion of Na+-rich aCSF versus aCSF increased CSF Na+ concentration to the same extent but caused severe versus mild hypertension in Dahl S and Dahl R rats, respectively. After central Na+ loading, hypothalamus "ouabain" significantly increased in Dahl S and only tended to increase in Dahl R rats. Moreover, sympathoexcitatory and pressor responses to intracerebroventricular exogenous ouabain were attenuated by Na+-rich aCSF to a greater extent in Dahl S versus Dahl R rats. Responses to air-jet stress or intracerebroventricular guanabenz were enhanced by Na+-rich aCSF in both strains, but the extent of enhancement was significantly larger in Dahl S versus Dahl R. Na+-rich aCSF impaired arterial baroreflex control of RSNA more markedly in Dahl S versus R rats. These findings indicate that genetic control of mechanisms linking CSF Na+ with brain "ouabain" is altered in Dahl S rats toward sympathetic hyperactivity and hypertension.

Adrenergic alpha-Agonists↗

PubMed2001

Responses to central Na(+) and ouabain are attenuated in transgenic rats deficient in brain angiotensinogen.

Studies with angiotensin (Ang) II type 1 receptor blockers suggest that the brain renin-angiotensin system contributes to sodium-induced sympathoexcitation and hypertension. To provide more specific evidence for the involvement of Ang II, locally produced in the brain, transgenic rats were used, which express an antisense RNA against angiotensinogen mRNA specifically in the brain, reducing angiotensinogen levels in the brain by >90%. In freely moving transgenic rats and Sprague-Dawley rats as control animals, blood pressure and heart rate responses to intracerebroventricular infusion (3.8 microL/min for 10 minutes) of artificial cerebrospinal fluid and Na(+)-rich artificial cerebrospinal fluid (containing 0.2, 0.3, and 0.45 mol/L Na(+)) as well as intracerebroventricular injection of ouabain (0.3 and 0.6 microgram/2 microL) were assessed. Central infusion of Na(+)-rich artificial cerebrospinal fluid increased blood pressure and heart rate in a dose-related manner. However, the peak increases by each dose of Na(+) were attenuated by 50% to 70% in the transgenic versus Sprague-Dawley rats. Increases in blood pressure and heart rate in response to ouabain at both doses were attenuated by 55% to 70% in the transgenic versus Sprague-Dawley rats. In the hypothalamus, Ang I level was markedly lower (31+/-9 versus 76+/-13 pg/g, P<0.05) and Ang II level tended to be lower in the transgenic versus Sprague-Dawley rats. These results indicate that the production of angiotensins in the brain is decreased in transgenic rats. The attenuated sympathoexcitatory and pressor responses to ouabain and Na(+)-rich artificial cerebrospinal fluid in transgenic rats support the concept that the local brain renin-angiotensin system, that is, locally produced Ang II, plays an important role in the sympathoexcitatory effects of ouabain and sodium.

Angiotensin I↗

PubMed2000

Resectional treatment for thyroid cancer with tracheal invasion: a long-term follow-up study.

HYPOTHESIS: Transmural invasion of the trachea by well-differentiated thyroid carcinomas is a locally advanced disease condition. It frequently causes deaths owing to airway obstruction. We hypothesized that resection of the invaded trachea followed by primary anastomosis provides the opportunity for cure. DESIGN: A retrospective review study of medical records. SETTING: The surgical department of a tertiary referral center. PATIENTS: Eight patients with well-differentiated thyroid carcinomas, complicated with tracheal invasion resulting in bleeding and airway obstruction, operated on by tracheal resection and immediate anastomosis, were included. INTERVENTIONS: All patients received total thyroidectomy and neck lymph node dissection as well as segmental tracheal resection followed by primary reconstruction. Postoperative radioactive sodium iodine I 131 treatment and suppression therapy with thyroxine were applied to all of them. MAIN OUTCOME MEASURE: Postoperative follow-up of serum levels of human thyroglobulin and abnormal radioactive iodine 131I from whole body scan. RESULTS: Seven patients are alive. Of these patients, 5 had no evidence of disease: (3 had no evidence of cancer for more than 10 years' follow-up), 2 had regional lymph node metastasis, and 1 had lung metastases. The remaining patient had anastomotic site recurrence with airway obstruction and needed tracheostomy to relieve stridor. She was lost to follow-up 39 months after undergoing the initial operation. CONCLUSIONS: Patients with mucosal invasion of the trachea by well-differentiated thyroid carcinomas should be treated by surgical resection followed by primary reconstruction when technically feasible. This facilitates postoperative care, and it is possible to achieve long-term survival with improvement of the quality of life and possible cures.

Adult↗

PubMed2000

Sympathoinhibitory and depressor responses to long-term infusion of nifedipine in spontaneously hypertensive rats on high-salt diet.

Short-term (by hour) intracerebroventricular (i.c.v.) or i.v. infusion of nifedipine at low rates evokes parallel decreases in renal sympathetic nerve activity (RSNA) and blood pressure (BP) in spontaneously hypertensive rats (SHR). In the present study, effects of long-term administration of nifedipine on BP and control of sympathetic tone were examined in SHR on a high-salt (8%) diet. From 6 to 8 weeks of age, for 2 weeks concomitant with taking a high-salt diet, rats were also treated with subcutaneous infusion of nifedipine at 10, 50, or 100 microg/kg/h or vehicle solvent as control using osmotic minipumps. At the end of the 2-week treatment period, mean arterial pressure (MAP), heart rate (HR), and RSNA at rest and in response to air-jet stress, i.c.v. injection of the alpha-adrenoceptor agonist guanabenz (25 microg), and i.v. injection of the ganglionic blocker hexamethonium were recorded in conscious rats. In rats on nifedipine 50 or 100 microg/kg/h, resting MAP was significantly lower (136+/-4 or 130+/-4 vs. 145+/-2 mm Hg in control rats, p < 0.05 for both), the sympathoinhibitory and depressor responses to i.c.v. guanabenz were significantly decreased, and the absolute decreases in MAP in response to i.v. injection of hexamethonium were significantly smaller. Sympathoexcitatory and pressor responses to air-jet stress, however, were not affected by nifedipine. Infusion of nifedipine at the three rates for 2 weeks caused concentrations of plasma nifedipine in a dose-related manner. Nifedipine was not detected in tissues of rats treated with 10 microg/kg/h nifedipine but was present in brain and other tissues of rats treated with nifedipine at the two higher rates. Thus in SHR on high-salt intake long-term treatment with nifedipine at 50 or 100 microg/kg/h decreased resting BP and the sympathetic component in BP control. In addition to possible peripheral effects, long-term administration of nifedipine may also act centrally to decrease sympathetic activity and BP, likely by increasing activity in central pathways involving sympathoinhibition, but not in pathways involving sympathoexcitation as evaluated by air-stress.

Animals↗

PubMed2000

Chronic blockade of brain "ouabain" prevents sympathetic hyper-reactivity and impairment of acute baroreflex resetting in rats with congestive heart failure.

In rats with congestive heart failure (CHF) post myocardial infarction (MI) acute blockade of brain "ouabain" reverses sympathetic hyperactivity and chronic blockade prevents the desensitization of baroreflex function. This study was conducted to determine: i) if chronic blockade of brain "ouabain" maintains normal sympathetic reactivity; and ii) if acute baroreflex resetting (another parameter of baroreflex function) also becomes impaired, and if so, does brain "ouabain" contribute to impairment in acute baroreflex resetting. CHF post MI was induced by acute coronary artery ligation in Wistar rats. Animals were treated with 200 microg x day(-1) i.c.v. or i.v. Fab fragments (which bind brain "ouabain" with high affinity), or treated with 200 microg x day(-1) i.c.v. gamma-globulins (control group). The length of treatment was 0.5-8 weeks or 4-8 weeks post MI. At 8 weeks mean arterial pressure (MAP), central venous pressure (CVP), heart rate (HR), and renal sympathetic nerve activity (RSNA) were recorded in concious rats at rest and in response to: i) air-jet stress, ii) i.c.v. guanabenz (an alpha2-adrenoceptor agonist), and iii) a 30 min i.v. infusion of nitroprusside (NP). Excitatory responses to air stress and inhibitory responses to guanabenz of MAP, HR, and RSNA were significantly enhanced in rats with CHF versus the sham-operated treated group. This enhancement was prevented in the CHF group treated with i.c.v., but not i.v., Fab. Nitroprusside induced a sustained decrease in MAP (approximately 25 mmHg) and a transient decrease in CVP. Heart rate and RSNA increased significantly within 1 min of beginning the infusion. The peak increases as well as the product of changes in MAP-HR and RSNA-HR were significantly smaller in rats with CHF treated with gamma-globulins versus sham rats and versus CHF rats treated with i.c.v. Fab. In sham-operated rats and CHF rats treated with i.c.v. Fab, RSNA and HR began to decrease within 3-4 min of beginning the NP infusion and had returned to baseline by 20 min. In contrast, RSNA and HR remained increased throughout the infusion in the CHF rats treated with gamma-globulins. These data indicate that in rats with CHF acute resetting of the arterial baroreflex in response to a lower BP becomes impaired, and chronic blockade of brain "ouabain" prevents both this change in baroreflex resetting as well as sympathetic hyperactivity.

Animals↗

PubMed2000

Sympathoinhibition by central and peripheral infusion of nifedipine in spontaneously hypertensive rats.

The present study assessed whether central mechanisms may contribute to the hypotensive effect of the calcium channel blocker nifedipine. In conscious, spontaneously hypertensive rats (SHR) on a high-salt diet, hemodynamic (mean arterial pressure [MAP] and heart rate) and sympathetic (renal sympathetic nerve activity) responses to low, central, intracerebroventricular infusion rates (25 microg. kg(-1). h(-1) for 2 hours) and peripheral intravenous rates (50 microg. kg(-1). h(-1) for 3 hours and then 100 microg. kg(-1). h(-1) for 2 hours) of nifedipine were evaluated. The distribution of nifedipine in the blood and tissues was assessed at the end of the infusions. Nifedipine significantly inhibited renal sympathetic nerve activity and lowered MAP in SHR beginning 30 minutes after the start of the intracerebroventricular infusion. The decrease of MAP by intravenous infusion began at 60 minutes and was more profound with 100 microg. kg(-1). h(-1). Inhibition of sympathetic activity preceded and then paralleled the decrease in blood pressure; it occurred earlier with central (15 to 30 minutes) than with peripheral (30 to 60 minutes) infusion. Intravenous infusion resulted in concentrations of nifedipine in brain structures (brain stem, midbrain, and cortex) that were 30% to 40% of those in the heart, kidneys, and liver. From the hemodynamic and sympathetic responses and the distribution of nifedipine into the central nervous system, we conclude that the peripheral infusion of nifedipine at relatively low rates may evoke a hypotensive response in SHR, not only via peripheral mechanisms, but also through central mechanisms, which will lead to an inhibition of sympathetic outflow and, therefore, a lowering of blood pressure.

Adrenal Glands↗

PubMed1999

Brain renin-angiotensin system and sympathetic hyperactivity in rats after myocardial infarction.

Blockade of brain "ouabain" prevents the sympathetic hyperactivity and impairment of baroreflex function in rats with congestive heart failure (CHF). Because brain "ouabain" may act by activating the brain renin-angiotensin system (RAS), the aim of the present study was to assess whether chronic treatment with the AT1-receptor blocker losartan given centrally normalizes the sympathetic hyperactivity and impairment of baroreflex function in Wistar rats with CHF postmyocardial infarction (MI). After left coronary artery ligation (2 or 6 wk), rats received either intracerebroventricular losartan (1 mg. kg-1. day-1, CHF-Los) or vehicle (CHF-Veh) by osmotic minipumps. To assess possible peripheral effects of intracerebroventricular losartan, one set of CHF rats received the same rate of losartan subcutaneously. Sham-operated rats served as control. After 2 wk of treatment, mean arterial pressure (MAP), heart rate (HR), and renal sympathetic nerve activity (RSNA) at rest and in response to air-jet stress and intracerebroventricular injection of the alpha2-adrenoceptor-agonist guanabenz were measured in conscious animals. Arterial baroreflex function was evaluated by ramp changes in MAP. Compared with sham groups, CHF-Veh groups showed impaired arterial baroreflex control of HR and RSNA, increased sympathoexcitatory and pressor responses to air-jet stress, and increased sympathoinhibitory and hypotensive responses to guanabenz. The latter is consistent with decreased activity in sympathoinhibitory pathways. Chronic intracerebroventricular infusion of losartan largely normalized these abnormalities. In CHF rats, the same rate of infusion of losartan subcutaneously was ineffective. In sham-operated rats, losartan intracerebroventricularly or subcutaneously did not affect sympathetic activity. We conclude that the chronic increase in sympathoexcitation, decrease in sympathoinhibition, and desensitized baroreflex function in CHF all appear to depend on the brain RAS, since this whole pattern of changes can be normalized by chronic central AT1-receptor blockade with losartan.

Angiotensin II↗

PubMed1999

Brain "ouabain" and angiotensin II contribute to cardiac dysfunction after myocardial infarction.

In chronic heart failure (CHF), sympathetic activity increases in parallel with the impairment of left ventricle (LV) function, and sympathetic hyperactivity has been postulated to contribute to the progression of heart failure. In the brain, compounds with ouabain-like activity ("ouabain," for brevity) and the renin-angiotensin system contribute to sympathetic hyperactivity in rats with CHF after myocardial infarction (MI). In the present studies, we assessed whether, in rats, chronic blockade of brain "ouabain" or the brain renin-angiotensin system inhibits the post-MI LV dysfunction. In rats, an MI was induced by acute coronary artery ligation. At either 0.5 or 4 wk post-MI, chronic treatment with Fab fragments for blocking brain "ouabain" or with losartan for blocking brain AT(1) receptors was started and continued until 8 wk post-MI using osmotic minipumps connected to intracerebroventricular cannulas. At 8 wk post-MI, in conscious rats, LV pressures were measured at rest and in response to volume and pressure overload, followed by LV passive pressure-volume curves in vitro. At 8 wk post-MI, control MI rats exhibited clear increases in LV end-diastolic pressure (LVEDP) at rest and in response to pressure and volume overload. LV pressure-volume curves in vitro showed a marked shift to the right. Intravenous administration of the Fab fragments or losartan at rates used for central blockade did not affect these parameters. In contrast, chronic central blockade with either Fab fragments or losartan significantly lowered LVEDP at rest (only in 0.5- to 8-wk groups) and particularly in response to pressure or volume overload. LV dilation, as assessed from LV pressure-volume curves, was also significantly inhibited. These results indicate that chronic blockade of brain "ouabain" or brain AT(1) receptors substantially inhibits development of LV dilation and dysfunction in rats post-MI.

Angiotensin II↗

PubMed1999

Sympathoinhibitory effects of central nifedipine in spontaneously hypertensive rats on high versus regular sodium intake.

-The putative central sympathoinhibitory actions of the dihydropyridine calcium antagonist nifedipine and the effect of dietary sodium on these actions were investigated in spontaneously hypertensive rats (SHR). Regular or high dietary salt was administered from 4 to 8 weeks of age. At 8 weeks, blood pressure (BP), heart rate (HR), and renal sympathetic nerve activity were recorded in conscious rats at rest as well as in response to intravenous (50 microg/kg) and intracerebroventricular (5 and 50 microg/kg) injections of nifedipine and intracerebroventricular injections of vehicle. Resting mean arterial pressure was higher in SHR on high versus regular salt (159+/-3 versus 135+/-4 mm Hg; P<0. 05). Nifedipine administered intracerebroventricularly decreased BP as well as renal sympathetic nerve activity and HR in a dose-related manner. The responses reached their peak at 3 to 5 minutes and lasted approximately 30 minutes. Peak decreases in BP, renal sympathetic nerve activity, and HR in response to both doses of nifedipine were significantly larger in SHR on high versus regular salt. Nifedipine administered intravenously also decreased BP but, in contrast, caused (reflex) increases in renal sympathetic nerve activity and HR. On both diets, intracerebroventricular vehicle did not affect mean arterial pressure, renal sympathetic nerve activity, or HR. These data indicate that in contrast to its peripheral vasodilator effect, centrally administered nifedipine may decrease sympathetic outflow and therefore BP and HR. The enhanced sympathoinhibitory and depressor responses to nifedipine in SHR on high versus regular salt suggest that the sympathetic hyperactivity induced by high salt intake is dependent on neuronal calcium influx via L-type channels.

Age Factors↗

PubMed1999

Brain renin-angiotensin system and ouabain-induced sympathetic hyperactivity and hypertension in Wistar rats.

In Dahl salt-sensitive rats on a high salt diet or normotensive rats with chronic central infusion of sodium, increased brain "ouabain" results in sympathetic hyperactivity and hypertension, possibly by activating the brain renin-angiotensin system. In the present study, we tested whether the hypertension caused by exogenous ouabain also depends on activation of brain renin-angiotensin system. In Wistar rats, ouabain (50 micrograms/d) was infused subcutaneously for 14 days with the use of osmotic minipumps. Concomitantly, in one group, the angiotensin II type 1 receptor blocker losartan (1 mg/kg per day) was infused intracerebroventricularly. On day 15, mean arterial pressure, heart rate, central venous pressure, and renal sympathetic nerve activity were recorded in conscious rats at rest and in response to air-jet stress, intracerebroventricular injection of the alpha(2)-agonist guanabenz (25 and 75 micrograms) or angiotensin II (30 ng), acute volume expansion, and ramp changes of blood pressure by +/-50 mm Hg with phenylephrine and nitroprusside. Compared with control rats, in rats treated with ouabain, resting mean arterial pressure was significantly increased (111+/-4 versus 93+/-3 mm Hg; P<0.05), and increases or decreases in mean arterial pressure, heart rate, and renal sympathetic nerve activity in response to air stress or guanabenz were enhanced significantly. These effects of ouabain were prevented when losartan was given concomitantly. Maximal slopes of arterial baroreflex control of renal sympathetic nerve activity and heart rate tended to be decreased in ouabain-treated versus control rats and were significantly increased in ouabain-treated rats with versus without losartan. No differences in cardiopulmonary baroreflex function were detected. It seems that by day 14 to 15, the central effect of ouabain on baroreflex control prevails over its peripheral sensitizing effect on baroreceptors, leading to a tendency of desensitization. These results indicate that chronic administration of ouabain activates the brain renin-angiotensin system, resulting in decreased sympathoinhibition and increased sympathoexcitation, impairment of baroreflex function, and hypertension.

Angiotensin II↗

PubMed1999

Digoxin prevents ouabain and high salt intake-induced hypertension in rats with sinoaortic denervation.

Digoxin prevents ouabain-induced hypertension in rats. In the present study, we tested whether this effect of digoxin depends on its sensitizing effect on baroreflex function or is due to an antagonistic action on exogenous ouabain or endogenous ouabain-like activity ("ouabain") in the brain. In Wistar rats, resting mean arterial pressure (MAP) was significantly increased by long-term subcutaneous (SC) ouabain (75 microg/d) plus high salt (8%) intake for 12 days (but not after only 5 days). In rats with chronic sinoaortic denervation (SAD), MAP was increased within 5 days of ouabain treatment to the same extent as MAP after 12 days of treatment in intact rats. The effect of ouabain and high salt was prevented when digoxin was given SC concomitantly via osmotic minipump (200 microg x kg(-1) x d(-1)). Resting MAP was not changed in rats treated with digoxin alone. In a second set of rats with chronic SAD or sham surgery, high salt intake was given for 14 days, with or without SC digoxin (200 microg x kg(-1) x d(-1)) or intracerebroventricular (ICV) antibody Fab fragments (200 microg/d), which bind "ouabain" with high affinity. On day 14, MAP, central venous pressure, heart rate, and renal sympathetic nerve activity were recorded in conscious rats at rest and in response to air-jet stress, IV phenylephrine and nitroprusside, and acute volume expansion with 5% dextrose IV. In rats with SAD versus sham surgery, high salt significantly increased resting MAP as well as excitatory responses of MAP, heart rate, and renal sympathetic nerve activity to air stress. These effects of high salt in rats with SAD were prevented by digoxin or Fab fragments. Arterial baroreflex function was blunted but cardiopulmonary baroreflex function was not affected in rats with SAD. Digoxin and Fab fragments had no effects on either function. In an in vitro assay for the inhibitory effects on Na+, K(+)-ATPase activity, 20 ng of ouabain caused 29% inhibition, but 20 ng of ouabain plus 13 or 53 ng of digoxin caused only 16% or 4% inhibition, respectively. These data indicate that the arterial baroreflex opposes sympathoexcitatory responses to ouabain and "ouabain" in the brain, thereby delaying ouabain- and preventing high salt-induced hypertension in Wistar rats. In addition to possible effects on the arterial baroreflex, digoxin appears to act centrally to prevent the sympathoexcitatory and pressor effects of increased brain "ouabain" or ouabain.

Animals↗

PubMed1999

Traumatic diaphragmatic hernia with delayed presentation.

BACKGROUND: Traumatic diaphragmatic rupture may occur in patients with thoracoabdominal injuries, and still poses a diagnostic challenge to surgeons. Those patients who survive the events without being diagnosed in the acute phase develop chronic traumatic diaphragmatic hernia. In this study, we reviewed cases of chronic traumatic diaphragmatic hernia managed over the past 35 years. METHODS: We retrospectively evaluated the clinical courses and radiologic images of 24 cases with chronic traumatic diaphragmatic hernia. RESULTS: Motor vehicle accident with blunt abdominal trauma was the most important mode of injury. Herniation was more common to the left plural cavity than to the right. The interval between injury and the onset of symptoms ranged from two weeks to 40 years (average, 7.3 years). Vague chest pain, shortness of breath, and bowel obstruction are the most common presentations. Chest radiographic findings suggested the diagnosis of diaphragmatic hernia in 20 patients. Barium study of the gastrointestinal tract was required to confirm the diagnosis. The most common herniated abdominal viscera were the stomach and colon. All patients received thoracotomy with reduction of hernia organs and closure of the diaphragmatic defect. The hospital course was uneventful with no operative mortality. CONCLUSIONS: Careful interpretation of radiographic images and early surgical intervention are essential in the management of patients with chronic traumatic diaphragmatic hernia. Thoracotomy with reduction of herniated organs can be performed safely with satisfactory results.

Adolescent↗

PubMed1999

Leiomyosarcoma of the gastric cardia and fundus.

BACKGROUND: Gastric leiomyosarcoma is rare among gastric malignancies, and only 20% of the cases are located in the gastric cardia or fundus. It has clinical manifestations different from tumors in other sites of the stomach. We reviewed cases of leiomyosarcoma of the gastric cardia or fundus to evaluate their clinicopathologic characters and patient survival. METHODS: From May, 1981, to June, 1998, a total of 15 patients who underwent curative resection of leiomyosarcoma of the gastric cardia or fundus were retrospectively identified and studied. All the clinical and pathologic data were reviewed and recorded. RESULTS: There were 11 men and four women. Their mean age was 59.1 years (range, 37-73 years). Tarry stools and epigastric fullness and pain were the most common symptoms, followed by body weight loss. All 15 patients had submucosal tumors in the gastric cardia or fundus, as shown by endoscopy, barium contrast radiography and computerized tomography. The incidence of esophageal involvement by the tumors was quite low. The mean tumor size was 10 cm, ranging from 4 cm to 20 cm. Locoregional organs were involved in nine patients. The median and mean survivals were 17.8 months and 31.7 months, respectively (range, 10.1-80.1 months) after curative resection. The three-year and five-year survival rates were 53% and 22%, respectively. CONCLUSIONS: The definitive preoperative diagnosis of the tumor is difficult before surgery, even though imaging studies show positive findings. Surgical resection with an adequate safe margin of normal tissue is the treatment of choice. Tumor size, serosal invasion with locoregional organ involvement and high tumor grade were the prognostic factors in the study.

Adult↗

PubMed1998

Brain "ouabain," ANG II, and sympathoexcitation by chronic central sodium loading in rats.

Both brain ouabain-like activity ("ouabain") and brain angiotensin II (ANG II) contribute to the sympathoexcitatory and pressor responses to high sodium intake in spontaneously hypertensive (SHR) and Dahl salt-sensitive (Dahl S) rats. To assess whether increases in cerebrospinal fluid (CSF) sodium can mimic this pattern of changes, Wistar rats were chronically infused with artificial CSF (aCSF) or sodium-rich aCSF (0.8 or 1.2 M sodium) intracerebroventricularly through osmotic minipumps for 14 days. Sodium-rich aCSF (0.8 M) was also infused intracerebroventricularly for 2 wk concomitantly with either antibody Fab fragments that bind ouabain and related steroids with high affinity, gamma-globulins as control (200 micrograms/day for both), or the AT1 blocker losartan (1 mg.kg-1.day-1). Sodium-rich aCSF increased CSF sodium from 146 +/- 2 to 152 +/- 2 (0.8 M) and 160 +/- 3 (1.2 M) mmol/l, and increased brain "ouabain" in the hypothalamus, pituitary, and pons. In conscious rats, sodium-rich aCSF increased baseline mean arterial pressure (MAP), enhanced MAP, heart rate (HR), and renal sympathetic nerve activity (RSNA) responses to intracerebroventricular alpha 2-adrenoceptor agonist guanabenz and air stress, and desensitized arterial and cardiopulmonary baroreflex control of HR and RSNA. These effects were largely prevented by intracerebroventricular Fab fragments or losartan. Thus, in Wistar rats, both brain "ouabain" and the brain renin-angiotensin system contribute to sympathoexcitation, impairment of baroreflexes, and hypertension caused by chronically increased CSF sodium. The similar patterns of changes caused by CSF sodium in Wistar rats and by high sodium intake in SHR and Dahl S rats indicate that if high sodium intake increases central sodium, such changes may contribute to sympathoexcitation and hypertension.

Adrenergic alpha-Agonists↗

PubMed1998

Both brain angiotensin II and "ouabain" contribute to sympathoexcitation and hypertension in Dahl S rats on high salt intake.

-Dahl salt-sensitive (Dahl S) and salt-resistant (Dahl R) rats from 5 to 9 weeks of age received a regular or high salt diet and concomitantly an intracerebroventricular infusion of the angiotensin type 1 blocker losartan (1 mg. kg-1. d-1) or antibody Fab fragments, which bind ouabain and related steroids with high affinity, or gamma-globulins as control (200 microg/d for both). At 9 weeks of age, blood pressure (BP), heart rate (HR), central venous pressure, and renal sympathetic nerve activity were recorded in conscious rats at rest and in response to air stress and to intracerebroventricular alpha2-agonist guanabenz (50 microg) and ouabain (0.5 microg). Baroreflex function was assessed by acute volume expansion with intravenous 5% dextrose and ramp changes of BP by +/-50 mm Hg induced by intravenous phenylephrine and sodium nitroprusside. In Dahl S but not R rats, high salt significantly increased BP and HR; enhanced BP, HR, and renal sympathetic nerve activity responses to air stress and guanabenz; and attenuated cardiopulmonary and arterial baroreflex control of renal sympathetic nerve activity and HR. Both losartan and Fab fragments prevented these responses to high salt to a similar extent in Dahl S rats but had no effect in Dahl R rats on high salt. Sympathoexcitatory responses to ouabain were attenuated in Dahl S on high versus regular salt and were abolished in Dahl R or S treated with losartan or Fab fragments. Consistent with previous studies in SHR, the present data indicate that in Dahl S on high salt, both brain "ouabain" and angiotensin II contribute to decreased sympathoinhibition and increased sympathoexcitation, impairment of baroreflex, and therefore hypertension.

Angiotensin II↗

PubMed1998

Brain "ouabain", a neurosteroid, mediates sympathetic hyperactivity in salt-sensitive hypertension.

This review addresses recent developments in the neurobiology of an endogenous inhibitor of brain Na+, K+ - ATPase, "ouabain". "Ouabain" is present in hypothalamic and medullary neurons and mediates sympathoexcitatory and pressor responses to acute and chronic increases in cerebrospinal fluid (CSF) sodium concentration as well as mediates the sympathoexcitatory and pressor responses to high dietary sodium intake in SHR and Dahl-S rats, and sympathetic hyperactivity in the congestive heart failure. Some of these actions of "ouabain" in the CNS take place in the median preoptic nucleus and ventral part of the AV3V region. Despite recent advances in unveiling a biological role for "ouabain" its structure, biosynthetic and metabolic pathways as well as actual control mechanisms remain unresolved.

Animals↗