In vivo and In vitro studies on the cerebrovascular dilatation induced by diazoxide in normotensive and renal hypertensive goats.

We studied the in vivo and in vitro effects of diazoxide on the cerebral circulation of 8 normotensive (mean arterial pressure = 100 mm Hg) and 5 renal hypertensive (mean arterial pressure = 146 mm Hg) goats. Injections of diazoxide (0.3-27 mg) into the internal maxillary artery of unanesthetized goats produced dose-dependent increases in cerebral blood flow (electromagnetic flowmeter), this effect being significantly higher in hypertensive goats. Intravenous injection of 5 mg/kg of diazoxide into normotensive goats increased cerebral blood flow 40 ml/min/100 g and mean arterial pressure dropped 22 mm Hg whereas in hypertensive goats cerebral blood flow was unchanged and mean arterial pressure decreased 50 mm Hg. The increase in heart rate due to intravenous diazoxide was similar in normotensive and hypertensive goats (35 beats/min). Cumulative applications of diazoxide (10(-5) to 10(-3)M) on isolated middle cerebral arteries produced dilatory responses both under resting conditions and after previous tonic contraction by serotonin. This relaxation was significantly greater in arterial segments from hypertensive goats. The results indicate that diazoxide exerts powerful dilatatory effects on cerebral vessels, both in vivo and in vitro, and that these effects are particularly evident in hypertensive animals.