Pharmacological studies on pinacidil, a new antihypertensive agent. (3). Studies on the vasodilating effects in isolated monkey arteries and the peripheral hypotensive mechanism in SHR.

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Abstract
Vasodilating effects of pinacidil in isolated monkey arteries were compared with those of nifedipine and hydralazine, and the relationship of the central nervous system to hypotensive and positive chronotropic effects of pinacidil in SHR was also studied. In arterial strips contracted with prostaglandin F2.alpha., the relaxant potencies of pinacidil were in the order of mesenteric = femoral > basilar = middle cerebral arteries, whereas those of nifedipine were middle cerebral = basilar = coronary > femoral arteries, and those of hydralazine were femoral > middle cerebral = coronary arteries. In pithed SHR, the hypotensive effect of pinacidil was dose-related, similar to hydralazine. Intravenous administration of 0.1 and 0.3 mg/kg of pinacidil in SHR demonstrated remarkable hypotension, whereas intracerebroventricular administration of the same doses did not show any significant effects. Therefore, the central autonomic nervous systems did not seem to take part in the hypotensive effects of pinacidil. The hypotension by intravenous administration of pinacidil in SHR was followed by an increase in heart rate. The increase in heart rate in conscious SHR was more marked than that in anaesthetized SHR. In pithed SHR, pinacidil did not show positive chronotropic effects even with the larger dose of 3 mg/kg, i.v. Propranolol pretreatment inhibited the increase in heart rate following hypotension produced by pinacidil were caused by the activation of efferent sympathetic nerves via the baroreceptor. The peripheral hypotensive mechanism of pinacidil was supported by the present results.