Pharmacological studies on pinacidil, a new anti-hypertensive agent. 1. Antihypertensive effects in SHR and DOC/saline hypertensive rats

Abstract

Antihypertensive effects of pinacidil (PND) were compared with those of hydralazine (HDL) and nifedipine (NFD) by determining the systolic blood pressure of the caudal arteries of conscious SHR and desoxycorticosterone (DOC)/saline hypertensive rats at temperatures between 29 degrees C to 30 degrees C using a newly developed tail cuff method. 1) A dose-dependent antihypertensive effect of PND in male SHR was observed in a dose exceeding 1 mg/kg, p.o. Comparison of antihypertensive effects during 6 hr after oral administration of antihypertensive agents showed that relative potencies of HDL and NFD to PND (1.0) were approximately 0.8 and 0.3, respectively. 2) Although no difference was observed in the antihypertensive effect of HDL between male and female SHR, these effects by PND and NFD were more potent in female SHR. 3) No tolerance was observed in the antihypertensive effect of PND by the once a day oral administration for 5 weeks in male SHR and DOC/saline hypertensive rats. Dose-dependent antihypertensive effects of PND in doses above 1 mg/kg were always observed during experimental periods. 4) In spite of the potent antihypertensive effects, pathological changes such as hyperplasia and hyalinization of arterial walls in kidneys in DOC/saline hypertensive rats were not improved by continuous administration of PND or HDL.