J. Baranes

The effects of PAF-acether on the cardiovascular system and their inhibition by a new highly specific PAF-acether receptor antagonist BN 52021

BN 52021, a new specific PAF-acether receptor antagonist, was evaluated on several cardiovascular models. BN 52021 antagonized PAF-acether-induced extravasation in rats. Inhibition of the hypotensive action of PAF-acether was obtained by administration of the antagonist, given preventively or curatively. In isolated guinea-pig hearts, BN 52021 inhibited the vasoconstriction induced by PAF-acether whereas a small inhibition was observed with papaverine. On the other hand, phosphodiesterase inhibitors were very effective against coronary vasoconstriction induced by vasopressin while BN 52021 was without effect. PAF-acether increased the tonus of rat isolated portal vein; this effect was inhibited by BN 52021, without any reduction in basal myogenic activity. In this model Ca2+ antagonists (D 600, diltiazem) showed a small inhibitory effect but they strongly reduced basal myogenic activity. Neither PAF-acether nor BN 52021 modified phenylephrine-induced contraction of the isolated rabbit aorta with or without endothelium demonstrating that endothelium-dependent relaxing factor is not related to PAF-acether. Our results suggest that BN 52021 specifically block the cardiovascular effects of PAF-acether. This agent may thus be an useful tool for a better understanding of the role of PAF-acether in hemodynamic changes involved in anaphylaxis or shock.

Antihypertensive profile of cicletanine, a furopyridine derivative: comparison with captopril, indapamide and prazosin.

The effects of cicletanine were compared with those of three other antihypertensive drugs: prazosin, a highly selective alpha 1 antagonist, captopril an angiotensin converting enzyme inhibitor and indapamide a diuretic antihypertensive agent, on young stroke-prone SHR rats with high salt diet; furthermore, vascular reactivity to cicletanine was studied on isolated rat aorta. At an equal dose (30 mg/kg per os) all the drugs prevent the onset of hypertension with the same intensity. The minimal effective dose on blood pressure was 1 mg/kg for both cicletanine and captopril, and 3 mg/kg for indapamide. The action on diuresis and electrolyte excretion occurs at a dose of cicletanine 10 to 30 times higher than that required to produce the anti-hypertensive effect. One of the possible mechanisms of the antihypertensive effects of cicletanine could be due to a direct action of the drug on the vascular wall. This vascular impact could be an interaction with the alpha-adrenoceptor system (apparent pA2 cicletanine = 5.12) or a decrease in the vascular spasmogenic response whatever agonist was studied.

Effects of diltiazem on renovascular-hypertensive and on normotensive rats

1. The effects of 10-min perfusions of diltiazem (o.1-2.5 mg/kg, i.v.) on arterial blood pressure were studied in anesthetized renovascular-hypertensive and in normotensive rats. 2. Diltiazem produced a dose-dependent decrease in blood pressure in hypertensive rats (ED50 congruent to 1 mg/kg). 3. Diltiazem also decreased blood pressure in normotensive rats, but this action was less sustained than in hypertensive rats. 4. These results support the contention that diltiazem might be useful for treating arterial hypertension.