Relaxation of isolated middle cerebral artery induced by diazoxide.
The effect of diazoxide on isometric tension of goat middle cerebral arteries was investigated both under resting conditions and under contraction produced by 10(-6) M serotonin. In addition, the inhibitory action of diazoxide was tested against contractile effects induced by different experimental interventions such as electrical field stimulation, norepinephrine, tyramine, histamine, and KCl. Diazoxide caused dose-dependent relaxation of cerebral arteries which was more pronounced when the vessels were previously contracted. High doses of diazoxide (10(-3) M) inhibited significantly the contraction induced by electrical field stimulation and all the vasoactive agents used. This inhibitory effect of diazoxide was greater for those drugs that directly or indirectly act through alpha-adrenergic receptor stimulation. Tritium release induced by electrical field stimulation of cerebral arteries previously labelled with 3H-norepinephrine was not affected in the presence of diazoxide. We conclude that diazoxide has a dilatory effect on goat brain vessels due to direct relaxation of smooth muscle together with a possible blockade of the alpha -adrenergic receptors. This effect might explain the maintenance of cerebral blood flow observed in vivo during diazoxide-induced arterial hypotension.
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D002536:Cerebral Arteries / Q000187:drug effects / Q000502:physiology*; D003981:Diazoxide / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005260:Female; D006041:Goats; D008564:Membrane Potentials / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects*; D009126:Muscle Relaxation / Q000187:drug effects*; D018377:Neurotransmitter Agents / Q000378:metabolism
D000959:Antihypertensive Agents; D018377:Neurotransmitter Agents; D003981:Diazoxide