Biomedical subjects

T Quesada

Publications and source records attributed to T Quesada.

At least 37 records · Page 2Linked to original sources

PubMed1994

N-acetyl-L-cysteine potentiates depressor response to captopril and enalaprilat in SHRs.

Recently, in vivo and in vitro studies have implicated nitric oxide as a mediator of the vascular effects of angiotensin-converting enzyme inhibitors (ACEIs). In the present study we hypothesized that N-acetyl-L-cysteine (NAC), by increasing the availability of reduced sulfhydryl groups, would enhance the antihypertensive response to the ACEIs captopril and enalaprilat by a mechanism dependent on nitric oxide. The experiments were performed on instrumented, indomethacin-pretreated, awake spontaneously hypertensive rats (SHRs). Thirty minutes after a bolus of captopril (10 mg/kg iv) was administered, blood pressure decreased from 167 +/- 5 to 147 +/- 6 mmHg (n = 8). The pretreatment with the donor of thiol groups NAC (300 mg/kg iv) potentiated the depressor response to captopril because blood pressure decreased from 172 +/- 3 to 139 +/- 4 mmHg (n = 6). At the dose of 60 micrograms/kg iv, the ACEI enalaprilat did not acutely modify the blood pressure of SHRs (from 172 +/- 5 to 167 +/- 4 mmHg; n = 6). However, when the SHRs were pretreated with NAC, the same dose of enalaprilat significantly reduced blood pressure from 176 +/- 5 to 151 +/- 5 mmHg (n = 6). This potentiation of the depressor response to ACEIs, due to NAC, was not observed when SHRs were pretreated with the nitric oxide inhibitor NG-nitro-L-arginine methyl ester (L-NAME; 50 micrograms.kg-1.min-1 iv). The results of this study suggest that NAC, a donor of sulfhydryl groups, potentiates the antihypertensive response to captopril and enalaprilat in SHR by a nitric oxide-dependent mechanism.

Acetylcysteine↗

PubMed1994

Renal effects of nitric oxide synthesis inhibition in cirrhotic rats.

In the present study, we have characterized the renal response to inhibition of endogenous nitric oxide (NO) synthesis [intravenous NG-nitro-L-arginine methyl ester (L-NAME) for 3 h] in anesthetized cirrhotic rats, with (ASC) and without (CIR) ascites, at doses that do not change blood pressure (BP). Administration of L-NAME induced opposite effects on water (UV) and sodium (UNaV) excretion in cirrhotic and control animals. Infusion of 1 microgram.kg-1.min-1 of L-NAME in CIR (n = 5) decreased renal plasma flow (RPF) at the end of the 3-h period, whereas UV, UNaV, and glomerular filtration rate (GFR) were unaltered. In contrast, infusion of L-NAME at 10 micrograms.kg-1.min-1 in six more CIR increased UV and UNaV significantly by the 1st h, without changes in BP or GFR, and these parameters remained elevated throughout the experiment. Infusion of 1 microgram.kg-1.min-1 in ASC (n = 6) did not change BP or GFR but significantly enhanced UV and UNaV after the 1st h. These effects were prevented by pretreatment with L-arginine (0.1 mg.kg-1.min-1) in another group of ASC infused with 1 microgram.kg-1.min-1 of L-NAME. These results indicate that, in ASC and CIR cirrhotic rats, inhibition of NO synthesis at nonpressor does improves renal excretion of sodium and water via a decrease in tubular reabsorption. NO is an important mediator of the renal excretory and hemodynamic alterations of experimental liver cirrhosis.

Amino Acid Oxidoreductases↗

PubMed1994

Renin and angiotensinogen mRNA expression in the kidneys of rats subjected to long-term bile duct ligation.

Activation of antinatriuretic systems such as the renin-angiotensin system, is of major importance in the pathogenesis of sodium retention in cirrhosis. In this study, we studied the intrarenal renin-angiotensin system by measuring renin and angiotensinogen mRNA expression in the kidney of rats subjected to long-term bile duct ligation in a phase before the development of ascites, when sodium retention is already present. Experiments were performed in sham-operated and bile duct-ligated rats 3 wk after surgery. Balance studies showed lower sodium excretion and greater sodium retention in the bile duct-ligated rats compared with the control animals. Plasma renin activity (4.41 +/- 1.01 ng Angiotensin I/ml/hr in the bile duct-ligated group vs. 4.20 +/- 0.74 in the controls) and plasma renin concentration were not different between the two groups. However, plasma renin substrate was significantly decreased in bile duct-ligated animals. Total kidney renin mRNA was significantly higher in the bile duct-ligated animals (0.83 +/- 0.14 densitometric units vs. 0.44 +/- 0.04 in the controls), as determined on Northern-blot analysis and densitometric quantitation. Angiotensinogen mRNA expression in the kidneys of bile duct-ligated rats was significantly decreased (0.09 +/- 0.01 densitometric units) compared with that of the controls (0.21 +/- 0.03). These results indicate that sodium-retaining, nonascitic bile duct-ligated rats show abnormalities of the intrarenal renin angiotensin system that precede changes in plasma renin activity. Our data suggest that the intrarenal renin angiotensin system may participate in the initiation of the renal pathophysiological abnormalities present in bile duct-ligated rats.

Angiotensinogen↗

PubMed1993

Reduced renal papillary plasma flow in non-ascitic cirrhotic rats.

1. The purpose of the present investigation was to determine whether an abnormality of the renal papillary circulation is present in a well-established model of cirrhosis without ascites (carbon tetrachloride/phenobarbital). 2. Compared with the control animals, cirrhotic rats showed a reduced diuretic (61.0 +/- 5.1 versus 18.0 +/- 2.5%) and natriuretic (67.8 +/- 8.3 versus 29.6 +/- 3.6%) response to a volume expansion (3% body weight infusion of 0.9% NaCl). The volume expansion-induced increase in renal interstitial hydrostatic pressure was also blunted in the cirrhotic rats (control 9.3 +/- 0.9 versus cirrhotic 6.1 +/- 1.0 mmHg) and there were no differences in mean arterial blood pressure, renal blood flow or glomerular filtration rate between control and cirrhotic animals. 3. Papillary plasma flow was determined by the 125I-albumin accumulation technique and expressed as ml min-1 100 g-1. In the basal state, papillary plasma flow was significantly lower in cirrhotic rats (59.1 +/- 4.4, n = 9) than in the control animals (81.8 +/- 6.9, n = 9). An isotonic saline expansion similar to the one described above significantly increased papillary plasma flow in control rats (108.4 +/- 9.1, n = 7) but did not change it in cirrhotic rats (60.2 +/- 4.9, n = 6). 4. Our results indicate the existence of a selective alteration in the renal papillary circulation in cirrhotic rats, both in the basal state and after a well-established vasodilatory stimulus.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Pressure diuresis and natriuresis in cirrhotic rats.

Arterial hypotension in liver cirrhosis has been proposed as a major mechanism contributing to renal sodium and water retention. To evaluate kidney excretory responses at different levels of arterial pressure (AP), we have characterized the relationships between renal perfusion pressure (RPP) and sodium and water excretion in carbon tetrachloride cirrhotic rats. Experiments were performed in anesthetized control (n = 9) and cirrhotic rats with (Asc, n = 6) and without ascites (Cir, n = 6) by mechanically adjusting vascular resistance in animals with renal denervation and infused with main systemic hormones. Control and Cir animals showed similar glomerular filtration rates (GFR), renal blood flows, hematocrits (Hct), and plasma proteins (PP). However, Hct, PP, and GFR were significantly lower in the Asc rats. For the same level of RPP, both cirrhotic groups excreted significantly less water and sodium than controls. Then, the pressure diuresis and natriuresis relationships of the Cir animals were significantly depressed, but those of the Asc animals were more reduced than those of the Cir rats. These results indicate that the cirrhotic kidney is not able to normally increase the sodium and water excretion in response to changes in AP. Intrarenal mechanisms, and not mainly RPP, are likely mediators of the renal alterations of liver cirrhosis.

Animals↗

PubMed1993

Role of prostaglandins on the renal effects of angiotensin and interstitial pressure during volume expansion.

This study was undertaken to determine, in anesthetized dogs, the role of renal prostaglandins (PG) in mediating the natriuretic response to increased renal interstitial hydrostatic pressure (RIHP) during extracellular volume expansion (ECVE) with isotonic saline. It was also determined if the intrarenal angiotensin II (ANG II) effects during ECVE are potentiated by the inhibition of PG synthesis. ECVE induced similar elevations of RIHP, natriuresis, and fractional lithium excretion in dogs treated (n = 7) and not treated with a PG synthesis inhibitor (n = 5). In other experimental groups, the effects of the intrarenal maintenance of ANG II levels (n = 6) by infusing captopril and ANG II into the right renal artery were compared with those induced by the simultaneous infusion of captopril, ANG II, and a PG synthesis inhibitor (n = 6). In response to ECVE, renal blood flow and glomerular filtration rate were similar in both kidneys when ANG II levels were maintained constant and were significantly higher in the left kidney when ANG II levels were maintained constant and PG synthesis was inhibited in the right kidney. However, when compared with the left kidney, the ECVE-induced increments of natriuresis and RIHP in the right kidney were reduced by the same magnitude when intrarenal ANG II was maintained constant with (36 and 53%, respectively) and without (40 and 54%, respectively) the simultaneous PG synthesis inhibition. Our results indicate that during ECVE, renal PGs do not play an important role in mediating the RIHP-induced increments in natriuresis and decrements in proximal sodium reabsorption. (ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗

PubMed1993

Salt-induced increase in arterial pressure during nitric oxide synthesis inhibition.

The objective of this study was to determine in conscious dogs the role of endothelium-derived nitric oxide in mediating the arterial pressure and renal response to a prolonged increment of sodium intake. After a control period of 3 days, an inhibitor of nitric oxide synthesis, NG-nitro-L-arginine-methyl ester, was infused intravenously during 5 consecutive days (0.1 micrograms/kg per minute). Sodium intake (80 mmol/d) did not change throughout the experiment in one group (n = 4). In another group (n = 6), 1 day after infusion of this inhibitor was started, sodium intake increased from 80 to 300 mmol/d during 4 consecutive days. Inhibition of nitric oxide synthesis in dogs with normal sodium intake induced a significant decrease in natriuresis and diuresis (P < .05) without changes in arterial pressure. However, in dogs treated with the nitric oxide synthesis inhibitor, mean arterial pressure increased from 95.2 +/- 3.3 to 106.2 +/- 4.0 mm Hg (P < .01) the first day that sodium intake was elevated and remained increased the following 3 days. In a different group of dogs (n = 5), the increment of sodium intake during 4 days did not induce changes in arterial pressure when nitric oxide synthesis was not inhibited. Cumulative sodium balance was higher (P < .01) in dogs treated simultaneously with the nitric oxide synthesis inhibitor and high sodium intake (158 +/- 21 mmol sodium) than in those treated only with the nitric oxide synthesis inhibitor (82 +/- 19 mmol sodium) or with high sodium intake (36 +/- 13 mmol sodium).(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

PubMed1992

Increased total vascular capacity in conscious cirrhotic rats.

The purpose of the present study was to determine the role of the systemic venous circulation in the hemodynamic alterations of the cirrhotic disease. Cardiac output (thermodilution; n = 8), mean circulatory filling pressure (balloon technique; n = 6), and blood volume (Evans blue dye; n = 7) were investigated in a rat model of liver cirrhosis without ascites induced by a 12-week individualized CCl4/phenobarbital treatment. Compared with control rats, conscious cirrhotic rats showed a hyperdynamic circulation characterized by normotension, high cardiac output (51 +/- 4.8 vs. 28.6 +/- 1.3 mL.min-1.100 g-1; P less than 0.01), and expanded blood volume (6.5 +/- 0.15 vs. 5.4 +/- 0.22 mL.100 g-1; P less than 0.05). There were no significant differences between control and cirrhotic rats in mean circulatory filling pressure (6.40 +/- 0.27 vs. 5.99 +/- 0.22 mm Hg, respectively) or in the pressure gradient for venous return (6.17 +/- 0.19 vs. 5.8 +/- 0.21 mm Hg, respectively). To further examine the venous tone, effective vascular compliance was estimated with the vascular filling-blood volume relationship by measuring the vascular filling before and after rapid changes in volume (+/- 8 mL.kg-1). Compliance was similar in both control and cirrhotic rats (3.15 +/- 0.26 and 3.41 +/- 0.21 mL.mm Hg-1), but the vascular filling-total blood volume relationship of the cirrhotic rats was displaced toward the volume axis. In conclusion, the increase in blood volume without changes in mean circulatory filling pressure (or venous tone) of the cirrhotic rats indicates a situation with venodilation and elevated total venous capacity; this is likely to be an important mechanism that could explain the hyperdynamic circulation of the cirrhotic disease.

Animals↗

PubMed1992

Role of nitric oxide in mediating renal response to volume expansion.

The objective of the present study was to determine the role of endothelium-derived nitric oxide in mediating the renal response to extracellular volume expansion with isotonic saline (5% body weight). In anesthetized dogs (n = 7) and before volume expansion, nitric oxide synthesis was inhibited in the right kidney by continuous intrarenal infusion of NG-nitro-L-arginine-methyl ester (1 microgram/kg/min). Arterial pressure and renal hemodynamics of both kidneys did not change significantly either during nitric oxide synthesis inhibition or during 5% volume expansion. However, in response to extracellular volume expansion, increases in natriuresis, diuresis, and fractional excretion of lithium (an index of proximal sodium reabsorption) were inhibited in the right kidney by 27%, 28%, and 41%, respectively, when compared with the contralateral kidney. Increases of renal interstitial hydrostatic pressure during 5% volume expansion were not statistically different between both kidneys. In another group of dogs (n = 4), the administration of L-arginine (0.5 mg/kg/min) into the right renal artery prevented the renal effects induced by the nitric oxide synthesis inhibitor during volume expansion. The findings in this study suggest that nitric oxide production plays an important role in regulating the renal response to extracellular volume expansion. The proximal tubule seems to be involved in the reduced renal excretory response to volume expansion during nitric oxide synthesis inhibition.

Animals↗

PubMed1992

Renal effects of prolonged synthesis inhibition of endothelium-derived nitric oxide.

The aim of the present study was to investigate in conscious dogs the long-term effects of nitric oxide synthesis inhibition on glomerular filtration rate, sodium and water excretion, and plasma levels of renin and aldosterone. After a control period of 3 days, an inhibitor of endothelium-derived nitric oxide synthesis, NG-nitro-L-arginine-methyl ester, was infused for 3 consecutive days at a dose (50 ng/kg/min) that did not induce significant changes in arterial pressure (n = 6). The inhibition of nitric oxide synthesis led to a large and sustained decrease (p less than 0.05) in glomerular filtration rate of approximately 35%. This change was accompanied by a decrease (p less than 0.05) in urinary sodium excretion from 78.9 +/- 4.6 meq/day to 49.8 +/- 6.8, 60.1 +/- 4.2, and 53.5 +/- 9.0 meq/day by days 1, 2, and 3 of nitric oxide synthesis inhibition, respectively. Changes in fractional sodium excretion failed to achieve statistical significance. Nitric oxide synthesis inhibition also induced a significant and sustained decrease in urine flow rate. The decrease in glomerular filtration rate, natriuresis, and diuresis was accompanied by a 45% increase in plasma renin activity (p less than 0.05) and no change in plasma aldosterone concentration. By day 3 of the recovery period, glomerular filtration rate, natriuresis, diuresis, and plasma renin activity returned to values similar to those found during the control period. The administration of L-arginine during 3 consecutive days (5 micrograms/kg.min i.v.) did not modify any of the parameters measured but effectively prevented all the renal changes induced by the 3 days of nitric oxide synthesis inhibition.(ABSTRACT TRUNCATED AT 250 WORDS)

Aldosterone↗

PubMed1991

Cardiocirculatory responses to AII and AVP in conscious rats.

Cardiac and peripheral circulatory responses to changes in afterload with angiotensin II (AII) and vasopressin (AVP) were investigated in ganglion-blocked (hexamethonium) conscious rats. Cardiac output (CO) was measured by thermodilution. Both hormones were infused at a dose adjusted to increase mean arterial pressure 70% above baseline. AVP (11.4 +/- 2.2 ng/kg/min, n = 6) decreased CO from 43.4 +/- 2.3 to 34.1 +/- 2.9 ml/min/100 g (p less than 0.001), whereas AII (33.4 +/- 7.4 ng/kg/min, n = 7) increased CO from 38.7 +/- 2.6 to 44.9 +/- 3.4 ml/min/100 g (p less than 0.01). Heart rate did not change with the increase in afterload with either vasoconstrictor. To study whether the different effects of AII and AVP on CO may be explained by their different actions on the venous system, changes in venous tone were evaluated by measuring mean circulatory filling pressure (MCFP) and determining the pressure gradient for venous return (PGVR). AVP changed neither MCFP nor PGVR, whereas AII increased both these parameters, 20.7 +/- 2.8% (p less than 0.01) and 20.3 +/- 6.4% (p less than 0.01), respectively, above control. We also examined the effects of AII and AVP on ventricular dynamics: left ventricular systolic pressure and left ventricular dP/dtmax increased as aortic pressure was increased in a similar manner with both vasoconstrictors. However, AVP induced a greater increase in left ventricular end diastolic pressure than AII. Our results indicate that AII induces an increase in preload by its effect on venous tone, which is adequate to increase cardiac output. The decrease in cardiac output induced by increasing afterload with AVP can be explained by two mechanisms: an inadequate venous return and a failure of the left ventricle to overcome the increased afterload.

Angiotensin II↗

PubMed1991

Limited cardiac preload reserve in conscious cirrhotic rats.

In conscious rats with experimental cirrhosis without ascites, we have studied whether there is a limited cardiac preload reserve by performing cardiac output (CO) curves. CO was determined by thermodilution at basal, 5, 7.5, and 10 cmH2O of right atrial pressure (RAP). RAP was elevated by dextran infusion (1 ml/min iv, 30 min). CO curves were performed by plotting changes in CO with changes in RAP. In the basal state, cirrhotic rats showed a hyperdynamic circulation defined by increased CO and stroke volume, decreased total peripheral resistances, and normotension without changes in heart rate. Blood volume was also elevated in cirrhotic rats compared with the control animals. Between the limits of RAP studied, the CO curve of control rats presented a typical ascending limb. In contrast, the CO curve of the cirrhotic animals showed first an ascending shifted upward limb and afterward a descending limb. These alterations were accompanied by changes in the inotropic state as measured as left ventricular (LV) peak dP/dt in hexamethonium-pretreated animals submitted to the same volume loads described above. With the same increases in RAP, LV dP/dt changed, in every group, in a manner similar to CO. The results of the present study indicate that cirrhotic rats with high blood volume and hyperdynamic circulation show, in the steady state, a limited preload reserve. The partial utilization of the preload reserve can make the cirrhotic heart unable to modulate cardiac performance with changes in loading conditions, thus determining a state of heart failure.

Animals↗

PubMed1991

Role of intrarenal angiotensin II in mediating renal response to volume expansion.

Natriuresis induced by extracellular volume expansion (ECVE) is accompanied by a decrease in renin release and by an increase of renal interstitial hydrostatic pressure (RIHP). This study was undertaken to examine, in anesthetized dogs, the relative role of intrarenal angiotensin II (ANG II) changes in mediating natriuresis, diuresis, and increases in RIHP induced by two different levels of volume expansion (1.5 and 5% body wt in 45 min) with isotonic saline. Intrarenal ANG II levels were maintained in the right kidney throughout the experiment by simultaneously infusing captopril (0.8 micrograms.kg-1.min-1) and ANG II (1 ng.kg-1.min-1) into the right renal artery. In response to 5% ECVE, increases in RIHP, natriuresis, and diuresis were inhibited in the right kidney by 55, 40, and 47% respectively, when compared with the left kidney. Significant increases occurred in plasma atrial natriuretic peptide (ANP) levels during 5% ECVE. Maintenance of constant intrarenal ANG II levels during 1.5% ECVE completely abolished the increment of RIHP and diuresis and inhibited the natriuretic response by 80% in the right kidney when compared with the left kidney. Plasma ANP levels did not change during the 1.5% ECVE. No differences between kidneys were found when the intrarenal effects of ANG II were blocked with saralasin before saline loading. These results suggest that increases in RIHP, natriuresis, and diuresis during ECVE are partially mediated by decreases in intrarenal ANG II levels. Furthermore, these results indicate that the role of intrarenal ANG II levels in mediating the renal response to ECVE is more important when plasma ANP levels do not change than when they are increased.

Angiotensin II↗

PubMed1991

Role of renin-angiotensin system in the impairment of baroreflex control of heart rate in renal hypertension.

Studies of the baroreceptor heart rate reflex were performed in two-kidney, one clip (2K1C) hypertensive rats to evaluate the relative importance of two factors--high blood pressure and high angiotensin II circulating levels--on impairment of the baroreflex, present in the acute phase of this model of hypertension. The sensitivity of baroreceptor reflex was determined by the slope of the relationship between changes in mean arterial pressure (MAP) and changes in heart rate in response to injections of phenylephrine and nitroprusside. Bradycardic and tachycardic responses were analyzed separately. In basal conditions, the slope of the MAP-heart rate relationship in 2K1C hypertensive animals was significantly lower than in control animals, both for tachycardic and bradycardic responses. Lowering of blood pressure with captopril to normotensive levels in the 2K1C animals significantly increased baroreflex gain in bradycardic responses to the level found in normotensive rats. Normalization of blood pressure with nitroprusside did not change baroreflex sensitivity. Infusion of angiotensin II at a dose that did not change MAP, previously normalized with captopril, completely reverted the effect of this agent on baroreflex sensitivity. Our data indicate that, in 2K1C hypertensive rats, decreased baroreflex sensitivity is mediated, at least in part, by high angiotensin II circulating levels. Elevated blood pressure per se is of secondary importance.

Angiotensin II↗

PubMed1991

Complications of CAPD in children: six years experience in Caracas, Venezuela.

Forty-three ESRD children received treatment with CAPD from November 1984 through July 1990. Mean patient age was 10 years (range 2-17 years) and total observation period (consolidated for the whole group) was 683 months. Double cuff Tenckhoff catheters were used as access. The most common complication was peritonitis with an overall rate of one episode per 5.6 patient/months. Important correlation was found between incidence of peritonitis and socioeconomic status assessed by Graffar Index (G.I.). Patients with lowest socioeconomic status (GI of IV and V) had one episode of peritonitis per 2.9 patient/months. Patients with GI of III had one episode per 5.2 patient/months and patients with the best socioeconomic status (GI of I and II) had only one episode per 11.6 patient/months. Other complications were the following: Infections: 18 exit site infection, 5 exit site granuloma and 5 tunnel abscess. Catheter malfunction: 17 obstructions, 5 migrations and 2 ruptures. Others: 3 peritoneal hemorrhages, 1 intestinal perforation, 3 eventrations, 4 inguinal hernias and 1 right pleural effusion. In this last patient, pleurodesis was unsuccessfully attempted with homologous blood. We conclude that patients with very low socioeconomic status are poor candidates for CAPD and should be considered preferably for hemodialysis.

Adolescent↗

PubMed1990

Effect of a chronic infusion of atrial natriuretic peptide on vascular reactivity in normotensive and renal hypertensive rats.

In a previous study, we found that a long-term infusion of atrial natriuretic peptide (ANP) produced a sustained reduction of mean arterial pressure and peripheral vascular resistance in two-kidney, one-clip (2K-1C) hypertensive rats, whereas in control rats it had only a transient effect on cardiac output. However, plasma levels of ANP were actually 3-fold higher in normotensive than in hypertensive rats. Previous studies suggested that plasma ANP levels might modulate the vascular reactivity to the peptide. The present study examined whether the lack of chronic hemodynamic effects of ANP in control rats was due to changes in vascular reactivity to the peptide. In control rats, vascular reactivity to ANP was reduced 50% by a chronic infusion of ANP. However, in 2K-1C hypertensive rats, a long-term infusion of ANP had no effect on the vascular reactivity to ANP. The results of the present study indicate that the lack of persistent hemodynamic effects of a chronic infusion of ANP in control rats may be due to a decrease in the vascular reactivity to the peptide. The sustained hypotensive and vasodilatory effects of a long-term infusion of ANP in 2K-1C hypertensive rats are associated with no changes in the vascular reactivity to ANP.

Animals↗

PubMed1990

Effect of a chronic infusion of atrial natriuretic peptide on sodium balance in normotensive and two-kidney, one-clip hypertensive rats.

We have previously found that chronic infusion of atrial natriuretic peptide (ANP) decreased mean arterial pressure (MAP) by 16% in two-kidney, one-clip (2K-1C) hypertensive rats, and we hypothesized that natriuresis might be modified through the pressure-natriuresis mechanism. We therefore decided to evaluate sodium balance in 2K-1C rats infused with ANP (0.5 micrograms/h for 4 days). The ANP infusion to the 2K-1C rats induced a significant decrease in MAP from 171 +/- 3 to a minimum value of 147 +/- 6 mm Hg after 2 days of treatment (p less than 0.001). Sodium excretion fell from 2,536 +/- 60 to 2,047 +/- 86 (p less than 0.001) and 2,211 +/- 96 mu Eq/24 h (p less than 0.05) by days 1 and 2 of ANP administration. Furthermore, fractional excretion of sodium intake decreased from 99.1 +/- 1.5 to 81.1 +/- 2.9 (p less than 0.001), 84.1 +/- 2.6 (p less than 0.05) and 85.9 +/- 5.15% (p less than 0.05) by days 1, 2 and 3 of ANP infusion, respectively, returning to basal values thereafter. The administration of vehicle (0.9% NaCl) did not induce any significant change in 2K-1C hypertensive rats. The infusion of either vehicle or the same dose of ANP to normotensive rats (0.5 micrograms/h, for 4 days) did not modify sodium balance throughout the experiment. These results strongly suggest that the ANP-induced decrease in MAP might be responsible for the transitory sodium retention observed in 2K-1C hypertensive rats during the administration of the peptide.

Animals↗

PubMed1990

Hemodynamic effects of long-term converting-enzyme inhibition in renal hypertensive rats.

The hemodynamic effects of a converting-enzyme inhibitor (CEI) given during 12 consecutive hours were studied in severe chronic renal hypertensive and normotensive Wistar rats. Hemodynamic parameters were obtained by thermodilution method in conscious unrestrained animals twenty-four hours after surgery. A bolus of CEI induced a significant decrease of mean arterial pressure (MAP) (from 192.2 +/- 8.2 to 163.3 +/- 5.9 mmHg, p less than 0.001) and total peripheral resistance (TPR) (from 7.69 +/- 0.53 to 5.83 +/- 0.33 mmHg.min/ml 100 g) in hypertensive animals. Cardiac index (CI) and heart rate increased significantly (p less than 0.05). Infusion of CEI to hypertensive animals during 12 consecutive hours produced a further progressive decrease in MAP and TPR (p less than 0.05) and an increase in CI (p less than 0.05). Heart rate did not change. Acute and prolonged infusions of CEI to normotensive group induced less but similar effect to those observed in hypertensive group. These results suggest that an increase of the renin-angiotensin system activity is the principal mechanism involved in the maintenance of high blood pressure during chronic phase of renal hypertension on the rats.

Angiotensin-Converting Enzyme Inhibitors↗