Analysis of cerebrovascular action of diazoxide in conscious goats.

Abstract

The effects of diazoxide on cerebral blood flow were evaluated in unanesthetized goats under control conditions and after selective blockade of adrenergic or cholinergic receptors in cerebral vessels. Injections of diazoxide (1-27 mg) into the internal maxillary artery produced dose-dependent increases in cerebral blood flow, an increase of 90% occurring with the highest dose. Administration of phentolamine, propranolol, or atropine into the internal maxillary artery did not modify the cerebrovascular response to diazoxide. In reserpine-treated animals the cerebral effects of diazoxide were also unchanged. Intravenous injections of diazoxide (150-400 mg) produced sustained hypotension and tachycardia whereas cerebral blood flow was maintained within normal values or increased slightly. The normal cerebral vasoconstriction obtained with injections of norepinephrine directly into the internal maxillary artery was unaffected during the diazoxide induced-hypotension. These findings show that diazoxide exerts a powerful vasodilatory effect on cerebral vessels through mechanisms other than blockade of alpha-adrenergic receptors or inhibition of adrenergic activity. The results also indicate that activation of beta-adrenergic or atropine-sensitive vascular receptors in the cerebral response to diazoxide is negligible.