Hydralazine: mode of action at the neuroarterial junction.
1. Hydralazine relaxes the rat tail artery by a direct action on vascular smooth muscle cells, which appears to be modulated by the action of sympathetic nerve terminals. 2. There is a gradient of response to hydralazine in arteries from normotensive Wistar rats, the proximal segments being poorly responsive. This gradient disappears after denervation with 6-hydroxydopamine in vitro. 3. Exogenously added purines inhibit noncompetitively the vasodilator response to hydralazine in denervated segments from normotensive Wistar rats. Their order of potency is 2-Cl-adenosine > adenosine > ATP > inosine. 4. The effect of hydralazine in innervated, poorly responsive segments is greatly potentiated by theophylline (50 mumol/l) and propranolol (5 mumol/l). These results, together with the effect of denervation, suggest that there are endogenous purines leaking from the nerve terminals under our experimental conditions. 5. Hydralazine produces a marked inhibition of stimulus-induced contraction and 3H release after [3H]noradrenaline loading. The mechanism of this prejunctional action appears to be different from the mechanism of the postjunctional effect.
D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000294:innervation; D004305:Dose-Response Relationship, Drug; D006830:Hydralazine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D006973:Hypertension / Q000503:physiopathology; D066298:In Vitro Techniques; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009469:Neuromuscular Junction / Q000187:drug effects*; D051381:Rats; D013806:Theophylline / Q000494:pharmacology
D006830:Hydralazine; D013806:Theophylline