Pre- and postjunctional actions of hydralazine in vascular and nonvascular smooth muscle in vitro.
This study investigated the in vitro prejunctional and postjunctional actions of hydralazine in vascular and nonvascular smooth muscle. Low concentrations (micromolar) of hydralazine blocked phenylephrine-induced increases in perfusion pressure in the innervated rat kidney, whereas high concentrations (greater than 10 microM) were required in the perfused, innervated rabbit ear artery. High concentrations of hydralazine were required to block phenylephrine-induced contractions of innervated rat vas deferens and anococcygeus muscle. After in vitro denervation, rabbit ear arteries became sensitive to low concentrations of hydralazine, but this was not observed in the rat vas deferens or anococcygeus muscle. Hydralazine (1-3 microM) was without effect on 3H-release from rat vas deferens, anococcygeus muscle and kidney previously incubated with [3H]norepinephrine. Hydralazine (1 microM) decreased field stimulation-induced 3H-release from [3H]norepinephrine-loaded rabbit ear arteries. The results from the rabbit ear artery confirm that in some vessels the presence of sympathetic nerve terminals can modify the postjunctional actions of low concentrations of hydralazine. However, the other vascular tissue studied (rat renal vascular bed) was sensitive to low concentrations of hydralazine while innervated. In conclusion, the existence of a postjunctional relaxant effect of hydralazine, observed in vitro at concentrations compatible with therapeutic blood levels found in humans, has been confirmed using two different vascular preparations. The relevance of the prejunctional effect of hydralazine remains to be ascertained.
D000818:Animals; D006830:Hydralazine / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009469:Neuromuscular Junction / Q000187:drug effects*; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013563:Sympathectomy, Chemical; D013997:Time Factors
D010656:Phenylephrine; D006830:Hydralazine