Search PubMed⌕ Search

Biomedical subjects

C Rosendorff

Publications and source records attributed to C Rosendorff.

At least 55 records · Page 3Linked to original sources
PubMed1985

Cardiovascular adrenoreceptor number and function in experimental hypertension in the baboon.

We studied adrenoreceptor density and affinity in the myocardial and pooled arterial smooth muscle membranes in a baboon model (Grollman 2-kidney, 2-figure-of-8) of hypertension, using tritiated prazosin (alpha 1-antagonist), yohimbine (alpha 2-antagonist) and dihydroalprenolol (beta-antagonist) as ligands. By the end of 24 weeks, mean arterial blood pressure had increased from 105 +/- 3 to 155 +/- 8 mm Hg, and heart rate increased from 102 +/- 6 to 118 +/- 2/min. In the myocardium, there was a significant decrease in alpha 2- and beta-receptor density, and significant decreases in alpha 1-, alpha 2- and beta-receptor KD values. In membranes from arteries, Bmax for alpha 1- and alpha 2-receptors more than doubled, with significantly increased Kd values for both receptor subtypes. The decrease in myocardial beta-receptor density may represent a down-regulatory response to the increased sympathetic activity in this type of hypertension, and the decreased Bmax for myocardial alpha 2-receptors may cause a decreased feedback inhibition of norepinephrine release from sympathetic nerve terminals, contributing to the increased heart rate. The increase in both alpha-receptor subtypes in arteries may be part of the pathogenesis of the hypertension. However, we were unable to show increased chronotropic responses to infused isoproterenol, or increased blood pressure responses to phenylephrine.

Animals↗
PubMed1985

Baboon erythrocyte ghosts contain beta-adrenergic receptors.

We have used the beta-adrenergic antagonist [3H]dihydroalprenolol [( 3H]DHA) to identify binding sites on the erythrocyte membrane of the primate Papio ursinus. Analysis of the saturation isotherm revealed binding to be saturable with a maximal number of binding sites of 499 fmol/mg protein. [3H]DHA binds specifically to the erythrocyte ghosts with an apparent dissociation constant (Kd) of 0.57 +/- 0.06 nM. A similar value for Kd (0.46 +/- 0.07 nM) was evaluated from the rate constants of association (0.013 +/- 0.003 X nM-1 X min-1) and dissociation (0.006 +/- 0.001 X min-1). beta-adrenergic agonists compete for the binding sites with an order of potency (dl-isoproterenol greater than l-epinephrine greater than l-norepinephrine) typical of a beta 2-adrenergic receptor. Binding was shown to be stereospecific with l-stereoisomers being more potent than their corresponding d-stereoisomers in causing half-maximal inhibition. Isoproterenol stimulated the production of intracellular adenosine 3',5'-cyclic monophosphate (cAMP) in a concentration-dependent manner, maximal levels (1.130 +/- 0.358 pmol cAMP/10(8) cells) being four times the basal levels. The results demonstrate the existence of a large number of beta-adrenergic receptors on baboon erythrocyte ghosts.

Animals↗
PubMed1985

Effects of coronary artery reperfusion on regional myocardial blood flow and function in conscious baboons.

The effects of coronary artery reperfusion initiated 1 hr and 3 hr after coronary artery occlusion were evaluated on measurements of overall and regional left ventricular function and on regional myocardial blood flow. These experiments were conducted in conscious baboons 2 to 3 weeks after recovery from instrumentation with a solid state left ventricular pressure gauge, aortic and left atrial catheters, a hydraulic occluder around the mid left anterior descending coronary artery, and pairs of ultrasonic transducers implanted in the endocardium of the left ventricular free wall or across the free wall to measure endocardial segment shortening and wall thickening, respectively. Coronary artery occlusion induced similar effects in both groups. At 1 hr after occlusion, the ischemic zone was characterized by severe and equal reductions in both endocardial (-97 +/- 1%) and epicardial (-95 +/- 4%) blood flows and complete loss of regional systolic function, which was replaced by paradoxical wall motion. Reperfusion initiated after 1 hr of ischemia was associated with a marked transient increase in endocardial (+386 +/- 51%) and epicardial (+544 +/- 79%) blood flows. During the subsequent 4 weeks, segment shortening and wall thickening tended to improve. However, at 4 weeks after reperfusion, segment shortening was still depressed by 45 +/- 12% and wall thickening by 58 +/- 14%. In contrast, reperfusion initiated after 3 hr of ischemia was not associated with a significant hyperemic response, and systolic segment shortening and wall thickening did not recover during the subsequent 4 week period.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Myocardial beta-receptors in experimental renal and aortic coarctation hypertensive rabbits.

We investigated the effect of inducing two-kidney, one clip (2K, 1C) and aortic coarctation (AC) hypertension in rabbits, on myocardial beta-adrenoreceptor number and affinity, using 3H-dihydroalprenolol as a beta-ligand. Six weeks after surgery, mean arterial blood pressures were: sham-operated controls C, 75.6 +/- 2.3 mmHg (n = 11); 2K-1C 96.3 +/- 2.5 mmHg (n = 6, P less than 0.005); and AC, 114.1 +/- 4.8 mmHg (n = 10, P less than 0.0005). Bmax values at six weeks for C, 2K,-1C and AC were 234.5 +/- 35.7, 139.0 +/- 10.3 (P less than 0.05) and 121.0 +/- 12.8 (P less than 0.005) fmol/mg protein respectively. There were no differences in KD. Both 2K, 1C and AC hypertension significantly decreased myocardial beta-receptor density; this may be a 'down-regulatory' response to increased circulating or myocardial catecholamine concentrations or to enhanced sympathetic activity.

Animals↗
PubMed1984

Effect of antihypertensive therapy on left ventricular function and myocardial perfusion at rest and during exercise.

We studied left ventricular function by equilibrium-gated technetium-99m ejection fraction and global left ventricular perfusion by thallium-201 scintigraphy in 43 patients with mild to moderate hypertension. Patients were studied at rest and during submaximal (approximately 50% of VO2 max) supine bicycle exercise, off therapy and on four forms of therapy for 16 weeks: methyldopa (n = 9); propranolol (n = 9); hydrochlorothiazide (n = 9); and enalapril (n = 16). None of the patients had focal myocardial ischaemia or heart failure. There were no differences between methyldopa, propranolol, hydrochlorothiazide and enalapril in blood pressure responses to exercise. However, heart rate at rest (57 +/- 4.6 beats/min) and during exercise (108 +/- 8.0 beats/min) was significantly lower in patients on propranolol than in other groups (70 +/- 3.9 and 117 +/- 5.5 beats/min for methyldopa; 75 +/- 3.3 and 119 +/- 4.9 beats/min for hydrochlorothiazide; 74 +/- 2.8 and 125 +/- 2.6 beats/min for enalapril). In the propranolol-treated group, mean ejection fraction fell from 55% at rest to 49% during exercise. This suggests that cardiac output is likely to be lower and peripheral resistance higher during exercise in patients on propranolol than on other forms of treatment. There were no significant differences in coronary perfusion responses to exercise, however, or in the ratio of coronary perfusion to rate-pressure product, between any of the groups. These findings suggest that the limitation in exercise tolerance often reported by patients on beta-blockers is not due to coronary insufficiency during exercise, but to an attenuation of the cardiac output response to exercise, together with a raised peripheral vascular resistance.

Adult↗
PubMed1982

Captopril--an overview.

Captopril (Capoten; Squibb) is a specific orally active antagonist of peptidyl-dipeptide carboxyhydrolase, the enzyme which converts angiotensin I to angiotensin II and which inactivates bradykinin. Captopril therefore reduces blood pressure in a variety of animal models of hypertension. In 96 studies on 1570 patients, captopril has been shown to be superior to placebo and equivalent to either propranolol or a diuretic in the treatment of essential hypertension. In the management of severe treatment-resistant hypertension, the response to captopril (alone or in combination with a diuretic and/or propranolol) was better than the response to standard triple therapy. Captopril, with digitalis and a diuretic, also improved the haemodynamic and clinical status of patients with refractory congestive heart failure. Side-effects include skin rashes (15%), proteinuria (1,1%, or 0,4% of patients with no prior renal disease) and the nephrotic syndrome (0,9%, or 0,3% of patients with no prior renal disease). Nearly all patients with the nephrotic syndrome in whom renal biopsies were performed were found to have membranous glomerulopathy. Neutropenia (total white cell count less than 1,000/microliter) was found in 33 of over 6,000 patients (0,4%), but in all cases there were other possible causes for this. Captopril is the first of an important group of antihypertensive and afterload-reducing drugs; its major indications are likely to be in the treatment of refractory severe hypertension or congestive heart failure.

Aged↗
PubMed1982

Guanabenz versus methyldopa in the therapy of mild-to-moderate hypertension.

The results of a double-blind cross-over study designed to evaluate the antihypertensive efficacy and safety of guanabenz versus methyldopa in mild-to-moderate essential hypertension are presented. Thirty patients were randomly assigned to a group receiving either guanabenz or methyldopa as initial therapy for 8 weeks, followed by a 2-week wash-out period; the patients then took the other trial medication for 8 weeks. There was a significant fall in both standing and supine systolic and diastolic blood pressures during each treatment period, but no statistically significant difference between the guanabenz and methyldopa periods. However, there was a significant difference between the two drugs as regards side-effects. In the guanabenz group 21% of patients stopped taking the drug because of side-effects or inefficacy compared with none of the patients in the methyldopa group. The overall incidence of adverse experiences was 76% for guanabenz and 50% for methyldopa. There was a statistically significantly greater incidence of dry mouth with guanabenz then with methyldopa, while drowsiness was common in both groups. It is concluded that guanabenz is as effective as methyldopa in the therapy of mild-to-moderate essential hypertension but that the side-effects, particularly dry mouth, will seriously limit its usefulness.

Adult↗
PubMed1982

Inhibition of adrenaline-forming enzyme in the brain prevents one-kidney, one-clip hypertension and deoxycorticosterone acetate-salt hypertension in the rabbit.

1. Phenylethanolamine N-methyltransferase (PNMT) converts noradrenaline into adrenaline and brain PNMT is elevated in spontaneously hypertensive and deoxycorticosterone acetate (DOCA)-salt hypertensive rats. In view of the evidence for the involvement of central adrenergic neurons in renal hypertension, we measured the blood pressure response in one-clip, one-kidney Goldblatt hypertensive and DOCA-salt hypertensive rabbits to the PNMT inhibitor SK&F 64139, injected into the lateral cerebral ventricles. 2. Intracerebroventricular injection of SK&F 64139 (10 micrograms/kg) significantly attenuated the mean arterial blood pressure rise in one-clip, one-kidney and DOCA-salt rabbits, at 4 and 8 weeks. 3. These findings support the idea the hypertension in this animal model required an intact adrenaline biosynthetic process, and that central catecholaminergic neurons may be involved in the pathogenesis of low-renin dependent forms of hypertension.

Animals↗
PubMed1982

Effects of tiapamil on haemodynamics and myocardial salvage during myocardial infarction in the baboon.

We studied the effects of tiapamil during myocardial infarction in the anaesthetized baboon. 10 animals received placebo and 8 animals the drug. After basal measurements the left anterior descending coronary artery was ligated. Measurements were repeated at 15 min and 2-hourly until the 12th h after occlusion. Placebo or drug (1 mg X kg-1 and 50 micrograms X kg-1 X min-1) was administered 20 min after occlusion. Tiapamil decreased afterload by reducing peripheral resistance. Blood flow to the peripheral ischaemic zone was increased. These effects resulted in myocardial salvage manifest as a reduction in serum creatine kinase (MB) isoenzyme levels and less myocardial damage at 12 h than that predicted for the placebo group by S-T segment mapping 15 min after occlusion.

Animals↗
PubMed1981

Cholesterol potentiates the coronary artery response to norepinephrine in anesthetized and conscious dogs.

We investigated the effect of hypercholesterolemia on coronary and cardiac hemodynamic responses to intracoronary norepinephrine (NE) (0.01 to 10.0 micrograms/min as the bitartrate) in a Gregg cannula autoperfusion system. Coronary blood flow was measured by the radioactive microsphere technique in two groups of open-chest dogs anesthetized with pentobarbital: 10 controls and 8 that were fed a cholesterol-rich diet (CD) which doubled the serum cholesterol level. In the control dogs, NE in doses of 0.01 to 1.0 micrograms/min had no effect on coronary vascular resistance (CVR) but 10 micrograms/min caused a significant decrease to 0.58 +/- 0.12 of control. In the CD dogs, NE at doses of 1.0 and 10.0 micrograms/min significantly reduced CVR, to 0.72 +/- 0.06 and 0.52 +/- 0.11 of control, respectively. There was no consistent effect of NE, at these doses, on myocardial oxygen uptake, left ventricular stroke work index, or maximal positive dP/dt. In a second series of experiments we measured coronary flow with electromagnetic flowmeters in 11 chronically instrumented conscious dogs, 5 controls, and 6 CD. In the control dogs, intravenously administered NE hydrochloride, 0.01 microgram/min, reduced CVR to 0.74 +/- 0.07 of control, and 1.0 microgram/min increased CVR to 1.26 +/- 0.09 of control. In the CD animals, these effects were seen at a 10-fold lower NE dose, 0.001 microgram/min (0.83 +/- 0.11 of control) and 0.1 microgram/min (1.32 +/- 0.06 of control). The vasodilation was blocked by propranolol, and vasoconstriction by phentolamine. We conclude that NE at low doses activates beta-adrenoreceptors to reduce CVR and at higher doses activates alpha-adrenoreceptors to increase CVR; the vasoconstrictor response is inhibited in pentobarbital anesthetized dogs, and hypercholesterolemia sensitizes coronary vessels to both the dilator and constrictor effects of NE.

Adrenergic beta-Antagonists↗
PubMed1980

Nephrotic syndrome during captopril therapy.

Captopril, an angiotensin-converting enzyme inhibitor, is being evaluated as an antihypertensive agent. We report on a patient who developed the nephrotic syndrome while on captopril 450 mg/d. Her urinary protein excretion was 5-7 g/24 h, plasma albumin concentration was 25 g/l, plasma cholesterol was 16,2 mmol/l, and she had oedema. Renal biopsy showed subepithelial deposits on the basement membrane.

Aged↗
PubMed1980

The treatment of mild to moderate essential hypertension with tienilic acid (ticrynafen).

This paper reports a clinical trial of tienilic acid, a new diuretic with uricosuric properties, in 23 patients with mild to moderate hypertension (standing diastolic blood pressure 90-120 mmHg). Tienilic acid was compared with hydrochlorothiazide in a variable-dose, double-blind cross-over study, and the duration of therapy was 8 weeks for each drug. The falls in blood pressure (systolic/diastolic) were: 11/11 mmHg supine and 17/11 mmHg standing for tienilic acid, and 8/12 mmHg supine and 9/17 mmHg standing for hydrochlorothiazide. There were no significant differences between the two drugs in their effect on blood pressure and heart rate, and regarding side-effects and laboratory results, except for serum uric levels (mean fall of 1,5 mg/dl with tienilic acid and mean increase of 1.1 mg/l with ydrochlorothiazide).

Clinical Trials as Topic↗
PubMed1980

Substance P increases hypothalamic blood flow via an indirect adrenergic-cholinergic interaction.

1 Hypothalamic blood flow (HBF) was measured in conscious rabbits by the 133xenon washout technique. 2 Substance P in a dose of 50 or 500 ng increases HBF while 5 ng is without effect. 3 Cholinoceptor blockade, with either atropine or mecamylamine abolishes the vasodilator effect of substance P. 4 Chemical sympathectomy of the hypothalamus with 6-hydroxydopamine, or adrenoceptor blockade with either propranolol or phenoxybenzamine abolishes the effect of substance P on HBF. 5 Destruction of the intracerebral noradrenergic pathway (INP), or blockade of its vasodilator action, with barbiturate or bicarbonate, likewise prevent the vasodilator action of substance P. 6 These results suggest that substance P may cause an increase in HBF via the release of endogenous acetylcholine, which in turn stimulates the INP.

Acetylcholine↗
PubMed1979

Haemodynamics of cardiac tamponade during various modes of ventilation.

Cardiac output and pleural, pericardial, arterial and cardiac pressures were measured in baboons during different modes of ventilation in the presence of acute cardiac tamponade. Fluctuations in pleural pressure during intermittent positive pressure ventilation were transmitted to the pericardial fluid. Cardiac output and transmural right ventricular end-diastolic pressure were significantly greater during spontaneous ventilation than during intermittent positive pressure ventilation with or without positive end-expiratory pressure. It is recommended that a patient undergoing surgery for cardiac tamponade be allowed to breathe spontaneously until the chest is opened and the pericardium incised.

Animals↗
PubMed1979

Evidence for an indirect cholinergic regulation of blood flow in the hypothalamus of conscious rabbits.

1 The effects of methacholine, atropine and adrenoceptor blockade on hypothalamic blood flow (HBF) were measured in conscious rabbits. 2 A dose of 1 microgram methacholine increased HBF while smaller and larger doses had no significant effect. 3 The vasodilatation induced by methacholine was blocked by atropine and by chemical sympathectomy of the hypothalamus with 6-hydroxydopamine. 4 The vasodilatation was reversed by propranolol but was not affected by phenoxybenzamine. 5 These results suggest that the vasodilator action of muscarinic receptor agonists on hypothalamic resistance vessels depends upon the integrity of a noradrenergic system, and is mediated via beta-adrenoceptors.

Animals↗