Showing papers by "Stéphane Laurent published in 1987"

Opposite central cardiovascular effects of nifedipine and BAY k 8644 in anesthetized rats.

Abstract: The central cardiovascular effects of the calcium channel blocker nifedipine and the calcium channel activator BAY k 8644 were studied in anesthetized and ventilated normotensive Wistar-Kyoto (WKY) or spontaneously hypertensive rats (SHR) Both drugs were administered in a 15-microliter volume into the lateral ventricle of the brain (icv) or into the cisterna magna (ic) The injection of vehicle alone (ic or icv) did not significantly change mean arterial pressure (MAP) or heart rate Nifedipine (5 and 50 micrograms/kg) and BAY k 8644 (5 and 50 micrograms/kg) induced opposite effects on MAP when centrally injected Nifedipine decreased MAP and induced a bradycardia (icv) or no change in heart rate (ic), and BAY k 8644 increased MAP without any significant change in heart rate (ic or icv) These effects were more marked with the highest dose of either drug These effects seemed to be of central origin, since they were suppressed by ganglionic blockade by hexamethonium (100 mg/kg iv), whereas after hexamethonium the hypotensive and the hypertensive responses to intravenously injected nifedipine and BAY k 8644, respectively, were preserved Bilateral vagotomy suppressed the bradycardia induced by icv administered nifedipine Previously icv administered nifedipine (5 micrograms/kg) antagonized the pressor response to BAY k 8644 (5 micrograms/kg icv) Changes in MAP and heart rate were significantly more marked in SHR than in WKY These results indicate that a calcium channel inhibitor and a calcium channel activator can modulate in opposite fashion central mechanisms involved in blood pressure control

Opposite central cardiovascular effects of nifedipine and BAY k 8644 in anesthetized rats.

Abstract: The central cardiovascular effects of the calcium channel inhibitor (CCI) nifedipine and the calcium channel activator BAY k 8644 (BAY) were studied in pentobarbital-anesthetized and ventilated normotensive Wistar-Kyoto (WKY) or spontaneously hypertensive rats (SHR). Both drugs were administered under a 1.5 microliter volume into the lateral ventricle of the brain (intracerebroventricular, i.c.v.). The injection of vehicle (ethanol) alone did not significantly change mean arterial pressure (MAP) or heart rate (HR). Nifedipine (5 and 50 micrograms/kg) and BAY (5 and 50 micrograms/kg) induced opposite effects on MAP when centrally injected. Nifedipine decreased MAP and HR while BAY increased MAP without significant change in HR. These effects are likely to be of central origin, because they were suppressed by ganglionic blockade with hexamethonium and by reserpine. Previously i.c.v. administered nifedipine (5 micrograms/kg) antagonized pressor response to BAY (5 micrograms/kg i.c.v.). Changes in MAP and HR were significantly more marked in SHR than in WKY. These results indicate that a calcium channel inhibitor and a calcium channel activator can modulate in opposite fashion central mechanisms involved in blood pressure control.

Hyperreactivity of the humeral artery to noradrenaline in essential hypertension patients

Abstract: The hyperresponsiveness of small arteries to norepinephrine is well documented in essential hypertensive patients. Our objective was to investigate in situ the reactivity to norepinephrine of the diameter of large arteries which are involved in the arterial disease of hypertension as well as small arteries. Brachial artery diameter, blood flow velocity, local volumic blood flow and local vascular resistances were determined non invasively using a pulsed Doppler system in 19 patients with essential hypertension and 9 normotensive subjects, before and after placebo (glucose) or increasing doses of norepinephrine (10, 20 and 40 ng/kg/min; i.v.) given in a single blind fashion. In hypertensive patients, norepinephrine (40 ng/kg/min) induced (i) a significant decrease in brachial artery diameter, local blood velocity, volumic flow and conductance and (ii) a small increase in mean arterial pressure. These hemodynamic changes did not occurred in the placebo group and were significantly greater in hypertensive patients than in normotensive subjects although plasma norepinephrine increased to the same extent in both groups. We conclude that in hypertensive patients, the increase in vascular reactivity to norepinephrine involves not only the resistive vessels, but also the large arteries thus decreasing their conducting and buffering function.

Intrinsic alterations of the arterial wall in hypertension and effect of antihypertensive therapy

Abstract: Therapeutic trials in hypertension indicate that cardiovascular morbidity and mortality are reduced by antihypertensive drug treatment but that the incidence of arterial ischaemic accidents remains elevated, in particular in the coronary circulation. Non-invasive haemodynamic studies in untreated uncomplicated hypertensive patients show that intrinsic alterations of large arterial vessels do exist in hypertension. These alterations involve reduced arterial compliance and hyper-responsiveness to vaso-constrictive stimuli. Various antihypertensive drugs causing the same blood pressure reduction act differently on large arterial vessels. Following drug therapy, arterial compliance may be increased (converting enzyme inhibitor) or decreased (dihydralazine). These findings may be relevant for the understanding of cardiovascular morbidity and mortality in patients treated for hypertension.

Vascular Compliance in Hypertension: Therapeutic Implications

Abstract: Vascular compliance is decreased in men with sustained essential hypertension. Reduced arterial compliance contributes to the maintenance of systolic pressure and end-systolic stress, thus participating in the development of cardiac hypertrophy. Reduced venous compliance contributes to maintaining the filling pressure of the heart in the presence of reduced intravascular volume. Reduced arterial and venous compliances are not the simple consequence of the elevated blood pressure but also reflect intrinsic alterations of the vascular wall. Thus, the blood pressure reduction due to antihypertensive agents is not constantly associated with a reversion of the decreased vascular compliance.