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Biomedical subjects

H R Keiser

Publications and source records attributed to H R Keiser.

At least 73 records · Page 4Linked to original sources
PubMed1990

Increased spillover of dopa into arterial blood during dietary salt loading.

1. We measured urinary excretion rates of dopamine (3,4-dihydroxyphenethylamine) and dopa (3,4-dihydroxyphenylalanine) and the spillover rate of dopa into arterial blood during dietary salt loading in conscious Dahl salt-sensitive and salt-resistant rats with intact or denervated kidneys. 2. Dopa spillover was calculated from the steady-state clearance of intravenously infused L-[3H]dopa and arterial levels of endogenous dopa. 3. Daily excretion rates of dopa and dopamine increased by about sixfold during salt loading in both rat strains. Bilateral renal denervation delayed these increases and the natriuretic responses. 4. During dietary salt loading, dopa spillover increased to approximately the same extent as simultaneously measured dopamine excretion. 5. The results suggest that increases in urinary excretion of dopamine during dietary salt loading can be accounted for by increases in the release of dopa into the bloodstream and that the renal nerves contribute to the dopa and dopamine excretory responses.

Animals↗
PubMed1990

Conscious atrial appendectomized rats have a blunted atrial natriuretic factor release to volume expansion but normal responses to other acute stimuli.

The release of atrial natriuretic factor (ANF) after various acute stimuli was studied in conscious chronic bilaterally atrial appendectomized (APP) rats. The response to acute volume expansion was markedly blunted (+67% v +357% in controls, P less than .01). However, the response to norepinephrine infusion was only moderately reduced (+107% v +212%, P less than .05) and the response to acute salt load was identical to that in normal controls (+148% v +180%, P = NS). These results demonstrate that APP rats can increase the secretion of ANF, at least to some acute stimuli. This indicates that the stores of ANF available for release are not significantly depleted after atrial appendectomy.

Animals↗
PubMed1990

The initial vasodilation and the later vasoconstriction of endothelin-1 are selective to specific vascular beds.

The regional hemodynamic effects of endothelin-1 (ET-1) were studied in Wistar-Kyoto rats. Endothelin-1 caused a transient increase in blood flow in the carotid and femoral arteries but a decrease in flow in the renal and mesenteric arteries. The resistance in the carotid and femoral beds decreased while it increased in the renal and mesenteric beds. Subsequently there was a variable increase in resistance in all vascular beds with a maximal increase in the renal bed. Thus, ET-1 initially causes a selective vasorelaxation in musculocutaneous beds but not in visceral beds; the cause of this selectivity is unknown.

Animals↗
PubMed1990

Surgical management of pheochromocytoma with the use of metyrosine.

Despite recommended preoperative preparation with alpha-adrenergic blockers, severe hemodynamic instability may occur during operations to resect pheochromocytoma. We combined the alpha-blocker phenoxybenzamine with the tyrosine hydroxylase inhibitor metyrosine in an attempt to better manage the hypertension of patients with pheochromocytoma undergoing surgical resection. This report reviews the cases of 25 consecutive patients undergoing surgery for known intra-abdominal pheochromocytoma. Each patient had elevated serum or urine levels of catecholamines or their metabolites. Nineteen patients were prepared before operation with phenoxybenzamine and metyrosine and six patients were given phenoxybenzamine alone. There were no significant differences in maximum, minimum, or mean blood pressure before or after tumor resection between patients who received metyrosine and those who did not. However careful review suggested that those who received metyrosine had more severe disease as judged by biochemical criteria. Study of selected patients matched for age and severity of disease suggested that the intraoperative blood pressure management of patients prepared with phenoxybenzamine and metyrosine was facilitated. In addition metyrosine-prepared patients lost less blood and required less volume replacement during surgery than did non-metyrosine-prepared patients. There were no apparent differences in postoperative fluid requirements. Although the study is not a prospective randomized trial, a retrospective review of patients managed with the combination of phenoxybenzamine and metyrosine suggests that surgery to resect pheochromocytoma can be better performed with both drugs than with phenoxybenzamine alone. The combination regimen appears to result in better blood pressure control, less blood loss, and the need for less intraoperative fluid replacement than does the traditional method of single-agent alpha-adrenergic blockade.

Adrenal Gland Neoplasms↗
PubMed1990

Angiotensin II and angiotensin converting enzyme binding in human adrenal gland and pheochromocytomas.

Binding sites for angiotensin II (Ang II) and angiotensin converting enzyme (ACE) were studied by autoradiography in human, rat and bovine adrenals and human pheochromocytomas. In human and rat adrenals, binding sites for both Ang II and ACE were found in the medulla and zona glomerulosa. In bovine adrenals, ACE binding sites were not detectable, while Ang II binding was higher in the zona glomerulosa, lower in the rest of the cortex and undetectable in the medulla. In pheochromocytomas, ACE binding was homogeneously distributed, but no Ang II binding was detected. These results suggest that circulating and/or locally formed Ang II could regulate adrenomedullary and zona glomerulosa functions in man, and show that chromaffin cells in tumors retain ACE binding sites but lose Ang II binding sites. Thus, there are alterations in the regulation of the renin-angiotensin system in chromaffin tumors.

Adrenal Gland Neoplasms↗
PubMed1990

Sodium intake modulates renal vascular reactivity to endothelin-1 in Dahl rats.

1. The systemic and renal haemodynamic responses to endothelin-1 (ET1) were evaluated and compared to Angiotensin II (AII) in anaesthetized Dahl salt-sensitive (DS) and salt-resistant (DR) rats on either low (0.1% NaCl in diet) or high (8% NaCl in diet) salt intake. 2. Baseline mean arterial pressure on low salt diet was similar in both strains, while on high salt diet it was 73 +/- 4 mmHg in DR rats and 119 +/- 8 mmHg in DS rats (P less than 0.05). Baseline renal blood flow (RBF) and renal vascular resistance (RVR) were similar in all groups. 3. AII in bolus injection induced a short, dose-dependent increase in blood pressure and renal vascular resistance and a fall in renal blood flow. The maximal pressure increase was significantly greater in DS rats on high salt diet than that in each of the other groups (P less than 0.05). The fall in renal blood flow and the increase in renal vascular resistance were attenuated in both strains on low salt diet. 4. ET1 induced an initial decrease followed by a prolonged increase in blood pressure; both phases were similar in all groups. However, renal vascular reactivity to ET1 was markedly modulated by salt intake. On low salt diet, following a bolus injection of ET1 (1 nmol/kg), RBF decreased by 34% in DR and by 20% in DS rats, while on high salt diet RBF decreased by 76% in DR and by 80% in DS rats (P less than 0.05 high vs low salt).(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1990

Atrial natriuretic factor (ANF 103-126) enhances volume- and pressor-induced heart rate response in the conscious rat.

The reduction in blood pressure due to ANF(103-126) fails to elicit reflex cardioacceleration in the conscious rat. To examine baroreflex sensitivity, the effect of ANF(103-126) on the heart period (HP) response to rapid central volume expansion and to alterations in mean arterial pressure (MAP) induced by bolus injections of phenylephrine and sodium nitroprusside was assessed. ANF(103-126) significantly augmented the bradycardic response induced by acute volume expansion from 426 +/- 21 to 391 +/- 23 beats min-1 versus 421 +/- 23 to 405 +/- 24 without ANF(103-126). Baroreflex sensitivity was defined by the ratio of the change in heart period to the maximal change in mean arterial pressure. The dose of ANF(103-126) utilized did not affect basal heart rate or the magnitude of the mean arterial pressure response to phenylephrine but did significantly enhance the nitroprusside-induced decrease in mean arterial pressure. Baroreceptor sensitivity to phenylephrine was significantly increased by ANF(103-126): 0.997 +/- 0.07 (ms mmHg-1) during ANF(103-126) vs 0.613 +/- 0.08 during vehicle. The total duration of the heart rate response to phenylephrine was also prolonged. In contrast, ANF(103-126) did not alter the baroreceptor sensitivity (1.45 +/- 0.3 vs 1.43 +/- 0.2 ms mmHg-1) or duration of heart rate response to nitroprusside. In the conscious rat, ANF(103-126) modifies the heart rate response to changes in mean arterial pressure and acute central volume expansion. This action appears to be dependent on stimulation of cardiac vagal afferents.

Animals↗
PubMed1990

Endothelin-induced vasoconstriction and release of atrial natriuretic peptides in the rat.

Endothelin-1 (ET-1) was given to male Sprague-Dawley rats in i.v. bolus injections to evaluate its effects on blood pressure and the release of atrial natriuretic peptides (ANP). In awake rats ET-1 (0.3, 1 and 3 nmol kg-1 body wt) transiently reduced mean arterial pressure (MAP) and increased heart rate (HR), followed by a prolonged increase in MAP. The magnitude of these changes and the duration of the increase in MAP were dose-related. The increase in MAP was completely blocked by verapamil, reversed by sodium nitroprusside, slightly reduced by rat atrial natriuretic factor (103-126) and unaffected by saralasin. The initial fall in MAP was also unaltered by these agents. In all groups HR changes were mirror-images of MAP. In anaesthetized rats ET-1 (1 nmol kg-1 body wt) induced a sustained release of ANP. Right atrial pressure increased transiently and then fell below baseline. When the increase in MAP was blocked with sodium nitroprusside, ET-1 still produced an increase in ANP. In conclusion we find that repeated i.v. administration of ET-1 induces immediate vasodilatation, without signs of tachyphylaxis, followed by long-lasting severe vasoconstriction. Baroreceptor function seems to be unchanged. ET-1 appears to induce ANP release by a direct action on atrial myocytes, independent of right atrial and systemic arterial pressure. We hypothesize that endothelin may be a mediator of stretch-induced release of ANP.

Animals↗
PubMed1990

Role of atrial appendages in modulating stimulated plasma atrial natriuretic peptide levels in conscious rats.

To evaluate the role of the atrial appendages in modulating plasma levels of atrial natriuretic peptide (ANP), we applied a series of both acute and chronic stimuli in conscious, chronic, bilaterally atrial-appendectomized (APP) and sham-operated control rats. Basal plasma ANP levels and urinary sodium excretion were normal in all rats after APP. The release of ANP was markedly blunted to acute volume expansion (+67% vs. +357% in controls, P less than 0.01) but was only moderately reduced after norepinephrine infusion (+106% vs. +212%, P less than 0.05) and was normal after acute salt load [+148% vs. +180% in controls, not significant (NS)]. Furthermore, plasma levels of ANP were increased normally in APP rats treated with deoxycorticosterone acetate (270 + 18 vs. 296 + 14 pg/ml in controls, NS) and in APP rats with congestive heart failure induced by a large arteriovenous (a-v) fistula between the aorta and the vena cava (306 +/- 18 vs. 302 +/- 12 pg/ml, NS). Sodium excretion patterns were similar in chronically stimulated APP and control rats. The results demonstrate that, although APP reduces the response of ANP release to acute volume expansion, it does not do so to other stimuli of either acute or chronic nature, suggesting that there is no permanent defect in the ability of APP rats to secrete ANP. These studies confirm that the atria are the major source for ANP release into the circulation after acute intravascular volume expansion. However, other tissue sources may contribute significantly to the levels of circulating ANP in response to this and other acute and chronic stimuli.

Animals↗
PubMed1989

Endothelin induces an initial increase in cardiac output associated with selective vasodilation in rats.

The systemic and regional hemodynamic effects of endothelin (ET), a novel endothelial derived vasoconstrictor peptide were studied in Wistar Kyoto rats. A bolus of 1 nmol/Kg ET intravenously induced a transient 43% decrease in blood pressure associated with a 57% decrease in systemic resistance and a 30% increase in cardiac output (p less than 0.01 for all parameters). This was followed by an increase of 20% in arterial pressure and of 71% in systemic resistance and a decrease of 30% in cardiac output at 10 minutes. The initial fall in blood pressure was not abolished by pretreatment with verapamil, captopril, indomethacin, ketanserin, atropine, methylene blue or ethanol. Verapamil abolished the hypertensive phase by markedly decreasing cardiac output. ET had selective effects on the arterial tree; during the hypotensive phase it caused a transient increase in blood flow in the carotid and femoral arteries (+41% and +83% respectively, p less than 0.01) but a decrease in flow in the renal and mesenteric arteries (-53% and -44% respectively, p less than 0.05). Accordingly, there was a decrease in resistance in the carotid and femoral beds (-55% and -67% respectively, p less than 0.01) and an increase in resistance in the renal and mesenteric beds (+102%; p less than 0.01 and +23%; p = N.S. respectively). Subsequently there was an increase in resistance in all vascular beds to variable degrees. The maximal increase in resistance was in the renal bed (+156%). Thus, ET causes initially a potent systemic vasorelaxation and an increase in cardiac output later progressing to systemic vasoconstriction and a decrease in cardiac output. The initial vasodilation is selective, appearing in musculocutaneous beds but not in visceral beds.

Animals↗
PubMed1989

Implications of plasma levels of catechols in the evaluation of sympathoadrenomedullary function.

This report summarizes new techniques for examining aspects of sympathoadrenomedullary function. Tracer pharmacokinetic methods are more accurate than measurements of antecubital venous norepinephrine (NE) in assessing sympathoneural responsiveness. During mental challenge (playing a video game), patients with essential hypertension had significantly larger increments of NE spillover into arterial blood than did normotensive control subjects, whereas responses of antecubital venous and even arterial NE did not differ significantly between the groups. The rate of neuronal reuptake of endogenous NE can be measured in vivo using plasma levels of NE and of the intraneuronal NE metabolite, dihydroxyphenylglycol (DHPG). Regional production of dihydroxyphenylalanine (DOPA) may reflect catecholamine biosynthesis, and DOPA may be an indirectly acting natriuretic neurohormone. Positron emission tomography after injection of positron-emitting fluorodopamine may allow in vivo, noninvasive assessments of regional sympathetic function.

Catechols↗
PubMed1989

Renal sympathetic nerve activity and norepinephrine release in rats.

We examined relationships between changes in directly recorded renal sympathetic nerve activity (RSNA) and renal and total body spillover of norepinephrine into the bloodstream (RNEs and TBNEs, respectively) in anesthetized, adrenal-demedullated rats. Intravenous infusions of nitroprusside (NP) or phenylephrine (PH) produced reflexive, dose-dependent changes in RSNA. High-doses of NP significantly increased RSNA by 90%, RNEs by 155%, and TBNEs by 268%. High doses of PH significantly decreased RSNA by 37%, RNEs by 35%, and TBNEs by 33%. Ganglionic blockade with chlorisondamine decreased RSNA by 65% (P less than 0.05), RNEs by 10%, and TBNEs by 51% (P less than 0.05). There was a significant curvilinear relationship between mean changes in RSNA and mean changes in RNEs (r = 0.99). Simultaneous in vivo measurement of sympathetic nerve traffic and regional release of norepinephrine therefore may be useful in the assessment of presynaptic actions of drugs and hormones and in the evaluation of abnormal sympathetic neurotransmission in disease states.

Afferent Pathways↗
PubMed1989

Normal atrial natriuretic peptide release after acute and chronic stimuli in hypophysectomized rats.

To test the hypothesis that the pituitary gland has a role in modulating the release of atrial natriuretic peptide (ANP) from atrial myocytes, we applied different stimuli of both acute and chronic nature to rats 8-10 days after hypophysectomy (Hypx). Acute rapid cardiac pacing at a rate of 500 beats/min in anesthetized rats caused a marked increase in plasma levels of ANP (from 76 +/- 7 to 237 +/- 60 pg/ml, P less than 0.05) despite a marked decrease of blood pressure. This response was similar to that of paced control rats, but because the basal levels were lower in Hypx rats, the relative increase in ANP was larger in the experimental group. Studies were also done in a chronic model of high-output congestive heart failure produced by an aortocaval fistula in hydrocortisone-supplemented rats. Although these rats had low blood pressure 2-3 days after surgery, there were marked increases in right atrial pressures associated with high plasma levels of ANP (194 +/- 24 pg/ml) that were not significantly different from controls (221 +/- 26 pg/ml, P greater than 0.05). These results indicate that the role of the pituitary in ANP release is indirect, and no specific hypophyseal factor is required for this response. Hemodynamic parameters are the important determinants of ANP secretion, even in hypophysectomized rats.

Animals↗
PubMed1989

Physiologic regulation and distribution of the renal vasopressin receptor.

Previous studies suggest that circulating levels of vasopressin (AVP) influence the responsiveness of the kidney to AVP. To determine how changes in renal AVP receptors and adenylate cyclase (AC) contribute to such altered responsiveness, we analyzed AVP receptors and AVP-sensitive AC in kidneys from Sprague-Dawley, Long-Evans and homozygous Brattleboro rats. In autoradiographic studies, the distribution of [3H]AVP binding sites was similar in all groups, corresponding to the location of AVP-sensitive AC: collecting ducts greater than outer medullary collecting ducts greater than medullary thick ascending limb greater than cortical collecting ducts. No differences in AVP receptor affinity or content were observed in kidney medullary membranes from Sprague-Dawley, Long-Evans or Brattleboro rats (KD = 0.8, 0.9, and 0.7 nM; Bmax = 116 +/- 9, 95 +/- 11 and 98 +/- 6 fmol/mg). Basal and AVP-stimulated AC activities were lower in kidney membranes from Brattleboro rats compared with Sprague-Dawley and Long-Evans animals (basal = 28 +/- 4, 40 +/- 4 and 38 +/- 3 pmol cAMP/mg/min; EDmax = 57 +/- 5, 80 +/- 7 and 71 +/- 2 pmol cAMP/mg/min) with no change in ED50. In 48-hour water-deprived Sprague-Dawley rats, AVP receptors were decreased from 116 +/- 9 to 58 +/- 2 fmol/mg, suggesting that AVP receptors are down-regulated by elevated AVP blood levels. The absence of changes in basal or AVP-stimulated AC in dehydrated rats indicates that receptor-AC coupling is normal and that maximum AC activation can occur with partial receptor occupancy. The data also indicate that impaired renal responsiveness to AVP in Brattleboro rats is not due to down-regulation of AVP receptors.

Adenylyl Cyclases↗
PubMed1989

Neuropeptide Y expression distinguishes malignant from benign pheochromocytoma.

No reliable gross or microscopic features distinguish benign from malignant pheochromocytomas. The diagnosis of malignant pheochromocytoma is based solely on the presence of regional or distant metastases. This study evaluated the expression of neuropeptide Y messenger RNA (mRNA) in nine benign and 11 malignant pheochromocytomas and has found that neuropeptide Y mRNA was expressed in all nine benign tumors but in only four of 11 malignant tumors (P = .0084). These data suggest that the determination of neuropeptide Y expression in the evaluation of patients with pheochromocytoma may have prognostic significance.

Adrenal Gland Neoplasms↗
PubMed1989

Pharmacologic and tracer methods to study sympathetic function in primary hypertension.

Systemically infused tritiated norepinephrine (NE) was used to estimate total body NE spillover into arterial blood during mental challenge (playing a video game) in 18 young (mean age 35 years old) patients with essential hypertension and 20 normotensives of similar age. Arterial NE, epinephrine (E), and total body NE spillover at baseline did not differ between the groups. During the game, total body NE spillover increased significantly in both groups, with the increments related directly to the pressor responses. Mean increments in total body NE spillover, arterial E, and mean arterial pressure were larger in the hypertensives (204 vs 91 ng/min, 33 vs 9 pg/ml, and 16 vs 12 mm Hg). The hypertensives increased total peripheral resistance during the game, whereas the normotensive group did not. Intravenous administration of yohimbine was used to increase NE spillover. Pressor responses to yohimbine were related to responses of arterial NE. The hypertensive group had a larger mean increment in blood pressure and arterial NE than did the normotensive group during yohimbine, due to excessive responses in a subgroup of about 1/3 of the patients. Patients with essential hypertension can have excessive sympathoadrenomedullary responsiveness related to excessive pressor responses, even when sympathoadrenomedullary activity at rest is normal.

Adult↗
PubMed1988

Calcium channel binding characteristics in the human heart.

The number, affinity, pharmacologic specificity and regional distribution of calcium channel binding sites in human hearts obtained at autopsy and open heart surgery were characterized using the radioligand [3H]nitrendipine. Scatchard analyses of saturation data from 6 autopsy hearts revealed a homogeneous distribution of high affinity binding sites (affinity-1 [KD] = 0.44 +/- 0.06, 0.52 +/- 0.07, 0.32 +/- 0.02, 0.30 +/- 0.03, and 0.45 +/- 0.01 nM; binding capacity [Bmax] = 30 +/- 4, 27 +/- 6, 25 +/- 7, 33 +/- 3, and 28 +/- 4 fmol/mg protein in right atrium, right ventricle, left atrium, left ventricle and ventricular septum, respectively). In ligand competition experiments, nifedipine and nitrendipine completely displaced binding with partial displacement by verapamil and 35% enhancement of binding by 10(-5) M diltiazem at 37 degrees. Analyses of right atrial appendages obtained at open heart surgery from 5 coronary artery bypass patients provided similar results (KD = 0.2 +/- 0.03 nM, Bmax = 42 +/- 2 fmol/mg protein). In addition, no significant differences in KD or Bmax were found in 3 hamster hearts assayed at the time of death or up to 18 hours postmortem at either 4 or 25 degrees. In contrast, there was a significant increase in Bmax (110 fmol/mg protein) with no change in KD (0.3 nM) in a myomectomy specimen from a patient with obstructive hypertrophic cardiomyopathy compared with either autopsy or surgical specimens. These studies illustrate the feasibility and potential advantages of studying calcium channels directly in human hearts.

Adult↗