Showing papers by "Stéphane Laurent published in 1989"

Calcium-entry blockers and arterial compliance in hypertension.

Abstract: Calcium-entry blockers dilate small arteries as well as large arteries, particularly in the brachial and the carotid circulations. This dilating effect is associated with an increase in systemic and brachial arterial compliance, which is poorly related to the level in blood pressure. Calcium-entry blockers are able to reverse the reduced arterial compliance observed in patients with essential hypertension, with important consequences to the structure and function of the heart and large vessels.

Endothelin has potent direct inotropic and chronotropic effects in cultured heart cells.

Abstract: To determine whether endothelin, a highly potent vasoconstrictor peptide, may affect cardiac myocyte contractility directly, we studied the effects of synthetic porcine endothelin-1 in cultured chick embryo ventricular cells. Endothelin-1 had a potent chronotropic effect (EC50 0.17 nmol/l) in spontaneously beating cells. The increase in the beating rate was accompanied by a frequency-dependent decrease in the amplitude of contraction. In electrically driven cells (1 Hz), endothelin-1 increased the amplitude of contraction dose-dependently, with an EC50 of 0.3 nmol/l, smaller than that of the calcium channel blocker BAY K 8644 (EC50 3.3 nmol/l), and with an efficacy close to that of BAY K 8644 and isoproterenol. Nicardipine (100 nmol/l) shifted to the right, by two orders of magnitude, the dose-response curve of endothelin-1 for inotropism. These results indicate that endothelin-1 is one of the most potent inotropic agents in cultured cardiac myocytes, and suggest that this effect involves, at least in part, a calcium ion influx through voltage-sensitive calcium channels.

Central cardiovascular effects of dihydropyridines in spontaneously hypertensive rats.

Abstract: Intracerebroventricular (i.c.v.) injections of dihydropyridine derivatives calcium channel agonist (BAY K8644) and antagonist (nifedipine, nicardipine, PN 200-110) induced opposite long-lasting changes in blood pressure (BP) in pentobarbital anesthetized spontaneously hypertensive rats (SMR). I.c.v. nifedipine (NIF), nicardipine (NIC), and PN 200-110 decreased mean blood pressure dose-dependently and stereoselectively, (+) NIC and (+) PN being 8 and 3 times more potent than their (-) isomers, respectively. The decrease in BP was due to a withdrawal of the sympathetic tone, since NIF- and NIC-induced falls in BP were suppressed after either hexamethonium (HXM), 6 OHDA or bilateral adrenalectomy. I.c.v. BAY K8644 increased BP dose-dependently. The i.c.v. BAY K8644-induced hypertensive effect was inhibited: a), by NIF and (+) PN but not by (-) PN, therefore probably occurring at central DHP sites; b), by HXM and reserpine, thus probably mediated by an increase in sympathetic tone; c) by i.c.v. methylatropine (MA) while i.v. MA and i.c.v. HXM had no inhibitory effect, thus probably involving central muscarinic sites. In SHR, NIC did not after the K(+)-evoked ACh release but suppressed the BAY K8644-induced increase in ACh release. In anesthetized normotensive control rats (WKY), neither i.c.v. NIF, NIC or BAY increased BP and HR while, in conscious SHR it decreased BP without any change in HR. These data increased BP and HR while, in conscious SHR it decreased BP without any change in HR. These data suggest that central DHP sites may be involved in the cholinergic transmission and may participate in genetic hypertension via sympathetic tone.

Large and small forearm arteries of essential hypertensives are less reactive to angiotensin II than to noradrenaline.

Abstract: In order to investigate the reactivity to angiotensin II (Ang II) in large and small arteries in situ, brachial artery diameter, blood flow velocity, local volumic blood flow and local vascular resistance (mean arterial pressure divided by local blood flow) were determined non-invasively, using a pulsed Doppler system. Increasing doses of Ang II (0.5, 1.0 and 2.0 ng/kg per min) were given intravenously and double-blind to nine normotensive subjects (group I) and 10 hypertensive patients (group III); placebo (glucose) was given to nine hypertensives (group II). Angiotensin II did not change the brachial artery diameter, blood flow velocity, local blood flow or local resistance. Mean arterial pressure was increased slightly but significantly (P less than 0.05) by Ang II at 2 ng/kg per min in groups I and III. In contrast, we had shown previously, following the same procedure, that subthreshold doses (for the increase in mean arterial pressure) of noradrenaline reduced branchial artery diameter, velocity and local blood flow and increased local resistance in hypertensives. These results indicate that in hypertensives the vascular reactivity of the brachial circulation (1) is lower than that of other territories in response to Ang II and (2) is lower in response to Ang II than in response to noradrenaline.

Effects of twenty-four hours of bed rest with head-down tilt on cardiopulmonary baroreflex control: preliminary study.

Abstract: The cardiopulmonary baroreflex response was studied before and after 24 h bed rest with head-down tilt (-5 degrees) in six normal male subjects, through lower body negative pressure (-5, -10, -15 mmHg) and passive leg raising. The reflex response was assessed (using plethysmography) by changes in forearm vascular resistance. During the lower body negative pressure and leg raising, forearm vasoconstriction and vasodilation were similar before and after head-down tilt. The study shows that orthostatic intolerance following head-down tilt is not explained by an abnormality in the response of low pressure baroreceptors.

Nicardipine decreases blood pressure and heart rate at nucleus tractus solitarii of spontaneously hypertensive rats.

Abstract: The effects of the dihydropyridine (DHP) calcium channel antagonist, nicardipine, on central cardiovascular regulation were investigated by injecting it into the cisterna magna or directly into the nucleus tractus solitarii (NTS), in anesthetized normotensive or spontaneously hypertensive (SHR) rats. Intracisternal injections of nicardipine (1-10 micrograms/kg) dose-dependently decreased blood pressure in SHR; there was no significant change in cardiovascular parameters in normotensive rats. In SHR, nicardipine (100 ng) microinjected bilaterally into the NTS produced hypotension and bradycardia. The same doses of nicardipine intravenously injected did not change either parameter. Previous administration of the beta-adrenoceptor blocking drug, tertatolol (50 micrograms/kg i.v.), prevented the nicardipine-induced bradycardia and hypotension after injection into the NTS. These data suggest that part of the central cardiovascular effects of nicardipine result from an interaction with DHP sites within the NTS leading to a withdrawal of the sympathetic tone.