Immediate central and peripheral haemodynamic effects of a new vasodilating agent Pinacidil (P1134) in hypertensive man

Abstract

The purpose of this study was to evaluate the immediate central and peripheral haemodynamic effects of a new vasodilating agent P 1134, in hypertensive man. After oral administration of 25 mg P 1134, the maximal haemodynamic changes were (mean +/- 1 SEM): mean blood pressure fell from 121.8 +/- 6.5 to 80.5 +/- 7.8 mmHg, heart rate increased 24.2 +/- 4.5 beats/min, cardiac output rose 2.9 +/- 0.3 1/min and forearm blood flow increased 1.0 +/- 0.1 ml/100 ml tissue/min. Stroke volume increased 17.0 +/- 2.1 ml and the inotropic state of the heart as judged from systolic time intervals increased. Total peripheral resistance and forearm vascular resistance were both reduced by approx. 50%. Linear correlations were found between the serum concentration of P 1134 and the change in mean blood pressure and total peripheral resistance. Changes in the other parameters mentioned above occurred progressively with changes in mean blood pressure and total peripheral resistance. It can be concluded that P 1134 is a very potent hypotensive agent with a haemodynamic profile identical to that seen with vasodilators with preferably act on precapillary resistance vessels. Potency and maximal efficacy exceeds that of hydralazine and seems like that of minoxidil. P 1134 is remarkably free from side-effects apart from causing water retention as all other vasodilators. It can be administered orally as well as intravenously. This makes P 1134 a very interesting compound in the treatment of moderate to severe hypertension, and further studies are well-founded.