Effects of the new calcium antagonist PN 200-110 on the myocardium and the regional peripheral circulation in anesthetized cats and dogs

Abstract

The effects of PN 200-110 (PN), isopropyl 4-(2,1,3- benzoxadiazol -4-yl)-1,4-dihydro-5-methoxycarbonyl-2,6-dim ethyl-3- pyridinecarboxylate , on the cardiovascular system were investigated. In chloralose-urethane-anesthetized cats PN decreased blood pressure (BP) and heart rate (HR) and increased cardiac output (CO) and total peripheral resistance dose dependently after intravenous doses of 1-10 micrograms/kg. Regional blood flow changes effected by an intravenous dose of 10 micrograms/kg were measured with microspheres. Flow to the heart, brain, and skeletal muscle increased selectively, and intramyocardial flow was redistributed in favor of the left ventricular subepicardial layer. The duration of action differed for various effects. The bradycardia was short lasting, and the cerebral vasodilatation persisted longest. It was not possible to predict the duration of action of PN on different target tissues by observing only one variable such as BP. Chloralose-urethane-anesthetized open-chest dogs appeared to be more sensitive to PN than cats. A dose of 3 micrograms/kg i.v. markedly increased coronary flow, lowered BP, increased CO, and tended to lower HR and to increase myocardial contractility. Myocardial oxygen consumption was lowered. PN did not alter diastolic excitation threshold or any electrocardiographic intervals in closed-chest anesthetized dogs. Absence of myocardial depression, potent vasodilator activity, and long duration of action might render PN useful for the treatment of hypertension and angina pectoris.