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Effects of pinacidil (PND) on the blood pressure of anesthetized cats and contraction of guinea-pig isolated hearts and blood vessels were compared with those of hydralazine (HDL) and nifedipine (NFD). PND showed a dose-dependent hypotensive effect and decrease of total peripheral resistance in a dose above 0.3 mg/kg (p.o.) in anesthetized cats. However, no involvement of the autonomic nervous system was presumed in the hypotensive effect of PND due to studies on autonomic responses. Although negative inotropic and chronotropic effects of PND in the isolated guinea-pig atria and heart (Langendorff method) were slight, PND caused a coronary vasodilation at a dose of 1 micrograms. PND inhibited the norepinephrine (NE) contracture of isolated guinea-pig thoracic aorta and portal vein at 10(-6)-10(-5) M, but concentrations of 10(-5)-10(-4) M were required for the inhibition of K contracture. In the isolated thoracic aorta, HDL markedly inhibited NE contracture, while NFD inhibited K contracture. These results suggest that the hypotensive effect of PND is more closely associated with the inhibition of Ca2+ influx caused by the receptor activation of Ca2+ release from intracellular storage sites than membrane potential-dependent Ca2+ influx.

Pharmacological studies on pinacidil, a new antihypertensive agent. 2. Studies on the hypotensive mechanism of pinacidil.