Pharmacological study of several effects of hydralazine in the bisected rat vas deferens.
We have studied several effects of hydralazine in the bisected rat vas deferens. Hydralazine produced a shift to the left of the concentration-response curve for noradrenaline, with potentiation of the maximal response in both portions of the vas deferens. In contrast it caused a shift to the right of the concentration-response curve for noradrenaline in preparations pretreated with cocaine (inhibitor of catecholamine neuronal uptake), and of the curve for methoxamine and for CaCl2 (in depolarizing medium with K+ 55 mM), in all cases with depression of the maximal response. Hydralazine enhanced the contractions induced by noradrenaline in Ca(2+)-free medium, except in the presence of cocaine. It had no effect on [3H]noradrenaline neuronal uptake into noradrenergic neurons of the vas deferens, nor did it affect basal or K(+)-induced 45Ca2+ uptake. These results suggest that hydralazine potentiates the contractions elicited by noradrenaline by a mechanism other than blockade of the neuronal uptake of this catecholamine. Our results also suggest that the inhibition by hydralazine of the contractions elicited by Ca2+ (in Ca(2+)-free depolarizing high-K+ 55 mM solution) and by methoxamine is not due to an action on voltage-dependent Ca2+ channels, but may reflect an intracellular site of action.
Campos-Toimil
M
M
Departamento de Farmacología, Facultad de Farmacia, Universidad de Santiago de Compostela, La Coruña, Spain.
Orallo
F
F
Gil-Longo
J
J
Verde
I
I
Loza
I
I
Fernández-Alzueta
A
A
D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000502:physiology; D002122:Calcium Chloride / Q000494:pharmacology; D002132:Calcium Radioisotopes; D003042:Cocaine / Q000494:pharmacology; D006830:Hydralazine / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D008729:Methoxamine / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014649:Vas Deferens / Q000187:drug effects / Q000378:metabolism
D002132:Calcium Radioisotopes; D006830:Hydralazine; D008729:Methoxamine; D003042:Cocaine; D002122:Calcium Chloride; D011188:Potassium; D002118:Calcium; D009638:Norepinephrine