SYSTEMIC AND CORONARY HEMODYNAMIC-EFFECTS OF PINACIDIL, A NEW ANTIHYPERTENSIVE AGENT, IN AWAKE DOGS - COMPARISON WITH HYDRALAZINE

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  • 1 January 1985
    • journal article
    • research article
    • Vol. 232  (2) , 369-375
Abstract
The systemic and coronary hemodynamic effects of 4 successive doses of pinacidil, a new experimental antihypertensive agent were compared with hydralazine in awake normal dogs. The 2 agents produced comparable dose-dependent decreases in total peripheral vascular resistance, but, compared to hydralazine, pinacidil had only a minor inotropic effect, as evidenced by the changes in cardiac output, left ventricular dP/dt [change in pressure with time] and dP/dt per P. Unlike hydralazine, pinacidil produced the changes only after aortic pressure had decreased significantly. The inotropic effects of pinacidil were abolished by propranolol pretreatment, suggesting that these effects are mediated by .beta. adrenergic receptors, probably secondary to sympathetic activation of the baroreceptor reflex. In addition, although myocardial O2 consumption and coronary blood flow were increased by both hydralazine and pinacidil, left ventricular work increased only after hydralazine administration. Coronary sinus O2 saturation increased to a much greater degree after pinacidil (from 20 .+-. 2-70 .+-. 4%) than after hydralazine and the fall in myocardial O2 extraction was greater with pinacidil, suggesting that pinacidil has a greater coronary vasodilator effect. The systemic and coronary vasodilator effects of pinacidil probably are not mediated via prostaglandins, .beta. receptor stimulation or adenosine because indomethacin, propranolol or aminophylline treatment had no effect upon its vascular effects. It appears that pinacidil differs from hydralazine in its mode of action and probably exerts its vasodilator effect by a direct action on vascular smooth muscle.

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