Characterization of the angiotensin II-receptor subtype in the longitudinal smooth muscle of the rat portal vein.

The purpose of the present study was to identify the angiotensin II-receptor subtype involved in the enhancement of the amplitude of the phasic contractions by angiotensin II in the isolated rat portal vein preparation. At an extracellular Ca2+ concentration of 0.9 mmol/l and a K+ concentration of 4 mmol/l, angiotensin II induced concentration-dependent increases in the amplitude of the phasic contractions.

Effects of manidipine and other calcium antagonists on rat renal arcuate arteries.

We investigated the effect of 1,4-dihydropyridine calcium antagonists (nifedipine, nisoldipine, and manidipine) on serotonin (5-hydroxytryptamine [5-HT])- and KCl (120 mmol/L)-induced contractions of rat isolated renal arcuate arteries. The preparation showed the well-known biphasic response to KCl-induced depolarization. All three calcium antagonists were more potent in inhibiting the second phase (tonic) compared with the first phase (transient) of the effect.

Protective effects of calcium antagonists in different organs and tissues.

The therapeutic efficacy of calcium antagonists in ischemic disorders of various tissues is attributed to vasodilator and antivasoconstrictor activities. A direct, energy-conserving, antiischemic effect of certain calcium antagonists has been claimed repeatedly by basic scientists. The clinical value of such effects has been doubtful until recently, when the organ-protective activity of certain calcium antagonists was confirmed in a few large-controlled clinical trials.

Cholera toxin but not pertussis toxin inhibits angiotensin II-enhanced contractions in the rat portal vein.

Angiotensin II (Ang II)-enhanced phasic contractions in the rat portal vein were concentration dependently inhibited by cholera toxin (0.1-10 micrograms/ml) and dibutyryl cyclic AMP (0.1-1 mM), but not by pertussis toxin (1 micrograms/ml), which suggests that Gi is not involved in the Ang II signal transduction pathway.

Mediation by the same muscarinic receptor subtype of phasic and tonic contractile activities in the rat isolated portal vein.

1. The effects of several agonists on the phasic and tonic contractile responses to muscarinic receptor stimulation have been investigated in the rat portal vein in vitro. 2.

Influence of the endothelium on Ca2+ dependency of angiotensin II-induced contractions of rat aortic rings.

Endothelium-dependent relaxation has been demonstrated to be involved in the regulation of vascular tone and extracellular Ca2+ was found to play a prominent role in this process. Since the dependency on extracellular Ca2+ appeared to differ considerably within the arterial tree, possibly as a consequence of vessel-related endothelium-dependent mechanisms, we investigated the effects of different compounds affecting Ca2+ entry (nifedipine, CoCl2) on angiotensin II-induced contractions of rat aortic rings with and without endothelium as well as the responses in a Ca(2+)-"free" solution. For this purpose, rat aortic rings were either undone from their endothelial layer by gentle mechanical rubbing or care was taken to keep the intima intact in case rings where endothelium were required.

Pharmacodynamic profile of carvedilol.

The combination of a beta blocker and a vasodilator is logical in the treatment of high blood pressure. Systemic arteriolar dilatation is beneficial to reduce the elevated peripheral resistance and hence to decrease cardiac afterload. beta-Adrenoceptor blockade exerts its own antihypertensive activity and also suppresses the reflex tachycardia induced by vasodilation.

Differential response of hypertrophied rat hearts to various alpha 1-adrenoceptor agonists.

With respect to the heart, the prolonged existence of hypertension, both in man and in experimental animals is predominantly characterized by an increase in left ventricular myocardial mass. In this process, the autonomic nervous system plays an important role. Although endogenous catecholamine stimulation of the heart is mainly exerted via the beta-adrenoceptors, in several mammalian species, the stimulation of cardiac alpha 1-adrenoceptors also mediates positive inotropic actions.

Cardioprotection by nifedipine in isolated working hearts: a comparative study on three different types of experimental ischemia.

Cardiac ischemia can be provoked by different methods in animal models and in isolated organs. Accordingly, three different procedures were followed to find the most sensitive model for the analysis of the anti-ischemic activity of calcium antagonists. The experiments were performed in the isolated working heart preparation of the rat, paced at the frequency of 5 Hz and perfused with Tyrode solution at 37 degrees C.

Comparative mechanisms of action of diuretic drugs in hypertension.

This review concerns the modes of action of thiazides, loop- and potassium-sparing diuretics, with particular emphasis on their antihypertensive activity. Thiazide diuretics inhibit an enzyme in the basolateral cell membrane in the distal tubule, thus bringing about an impaired absorption and enhanced excretion of both Na+ and Cl- ions. The loss of Na+ ions is countered by the exchange from Na+ against K+, hence causing a loss of K+ ions.

Characterization of the muscarinic receptor subtype mediating vasodilation in the rat perfused mesenteric vascular bed preparation.

1. The nature of the muscarinic receptor subtype mediating endothelium-dependent vascular relaxation was investigated in the perfused mesenteric vascular bed preparation which is a model for resistance vessels. 2.

Development and trends in the drug treatment of essential hypertension.

Aim: A brief survey is given of the development of the drug therapy of essential hypertension over five decades, followed by a discussion on newer antihypertensive drugs and principles.

Drugs That Modulate The Sympathetic Nervous System: Virtually all levels and elements of the sympathetic nervous system can be modulated by drugs in such a manner that elevated blood pressure is lowered, for instance with the use of central alpha 2-adrenoceptor agonists (clonidine, alpha-methyldopa), ganglioplegic drugs, peripheral adrenergic neurone blockers, and alpha- and beta-adrenoceptor antagonists. The beta-blockers have been maintained as a very major group of antihypertensive therapeutics.

Impaired vasodilator and chronotropic responses to 5-hydroxytryptamine in two models of hypertension-associated cardiac hypertrophy.

Objective: In connection with hypertension, research concerning 5-hydroxytryptamine (5-HT) receptors and subtypes in the cardiovascular system has so far been predominantly focused on various vascular tissues. In this study, the effects of 5-HT were investigated in isolated hearts with experimental cardiac hypertrophy.

Design And Methods: Cardiac hypertrophy was induced by stenosing the abdominal aorta (ASR) of 5-week-old Wistar rats.

Depressed inotropic response to beta-adrenoceptor agonists in the presence of advanced cardiac hypertrophy in hearts from rats with induced aortic stenosis and from spontaneously hypertensive rats.

Objective: To study the inotropic response to beta-adrenoceptor stimulation in isolated hypertrophied hearts from hypertensive rats.

Design And Methods: Cardiac hypertrophy was induced in Wistar rats by stenosing the abdominal aorta. Functional responses to isoprenaline, dobutamine, terbutaline and salbutamol were measured in paced (5 Hz), aortically stenosed hearts (18-20 and 32-34 weeks of age) and compared with those of sham-operated spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats.

Enhanced inotropic responsiveness to alpha 1-adrenoceptor stimulation in isolated working hearts from diabetic rats.

We compared the inotropic responsiveness to the alpha 1-adrenoceptor agonist cirazoline and the calcium entry promoter Bay K 8644 in isolated working hearts from streptozotocin (STZ) diabetic rats and age-matched controls. The maximal rate of contraction and cardiac output (CO) were unaffected by diabetes. The maximal rate of relaxation was significantly decreased in diabetic hearts as compared with controls.

Differential effects of alpha 1- and alpha 2-adrenoceptor agonists on peripheral vasoconstriction in pithed diabetic rats.

The pressor responses to selective alpha 1-adrenoceptor agonists (cirazoline and methoxamine) and to alpha 2-adrenoceptor agonists (UK-14,304 and B-HT 933) were investigated in pithed, streptozotocin-induced diabetic rats and age-matched control animals. Three months after induction of diabetes, the basal values of diastolic blood pressure (DBP) were the same in pithed diabetic and control rats (34.3 +/- 4.

The Rational for the Use of à -Blockers in the Treatment of Congestive Heart Failure.

Limited clinical data suggest that in particular types of congestive heart failure, the cautious use of low-dose à -blockers may be beneficial, despite the well-known cardiodepressant effect of these drugs. Downregulation of cardiac à -adrenoceptors has been demonstrated repeatedly in various forms of congestive heart failure. This phenomenon is caused by the long-term exposure of these receptors to endogenous noradrenaline (a à -adrenoceptor agonist), which is known to reach markedly elevated plasma concentrations in severe congestive heart failure.

[Pharmacologic profile of urapidil. Consequences for use as an antihypertensive drug].

Urapidil, a phenylpiperazine-substituted derivative of uracil, is an example of an anti-hypertensive which lowers elevated blood pressure via at least two different mechanisms. As such, it belongs to the multifactorial or hybrid anti-hypertensives. Urapidil is a peripherally acting alpha 1-adrenoceptor antagonist, and, in this regard, is comparable with prazosin and its successor compounds (e.

Serotonergic receptors and drugs in hypertension.

The possible role of 5-hydroxytryptamine (5HT) and 5HT-receptors in hypertension, already suggested by Page in 1954, has been subject to a renaissance of interest owing to the development of antihypertensive drugs which interact with 5HT-receptors. These drugs, like ketanserin, urapidil and flesinoxan are used as tools to study the role of 5HT and its receptors in hypertension. Some arguments would plead in favour of a certain role of 5HT and 5HT-receptors in the pathogenesis and maintenance of hypertension: hyperresponsiveness of blood vessels from hypertensive patients and animals to 5HT-induced constriction; the antihypertensive/vasodilator activity of the 5HT2-receptor antagonist ketanserin; enhanced sensitivity of platelets from hypertensives to 5HT.

Alpha 1-adrenoceptor-mediated Ca(2+)-entry from the extracellular fluid and Ca(2+)-release from intracellular stores: no role for alpha 1A,B-adrenoceptor subtypes in the pithed rat.

1. In the present study, we tested the hypothesis that in the pithed rat preparation two subtypes of the alpha 1-adrenoceptor are linked to two different signal transduction mechanisms, both of which contribute to vasoconstriction, one facilitating Ca(2+)-entry from the extracellular fluid (alpha 1A) and one promoting the release of Ca2+ from intracellular sources (alpha 1B). 2.

A girl with 71,XXXXY karyotype.

A girl with a 71,XXXXY karyotype is described. Internal and external genitalia were female despite the presence of a Y-chromosome.