Effects of alpha-adrenoceptor antagonists on electrical and mechanical responses of the isolated dog mesenteric vein to perivascular nerve stimulation and exogenous noradrenaline.

The effects of four different alpha-adrenoceptor antagonists (prazosin, phentolamine, yohimbine, and nipradilol) on the electrical and mechanical responses of smooth muscle cells of the dog isolated mesenteric vein to perivascular nerve stimulation and exogenous noradrenaline were investigated. Perivascular nerve stimulation generated an excitatory junction potential (e.j.p.), a spike potential and a slow depolarization. The latter component was blocked by yohimbine or phentolamine at doses over 10(-7) M, while the former two components were suppressed by 10(-6)-10(-5) M yohimbine, but not by prazosin, nipradilol or phentolamine (up to 10(-5) M). Nerve-mediated muscle contractions were suppressed by these alpha-adrenoceptor antagonists in a concentration-dependent manner, at doses over 10(-7) M. The order of potency was yohimbine greater than nipradilol = phentolamine greater than prazosin. Exogenously applied noradrenaline (10(-6) M) depolarized the smooth muscle membrane and generated slow waves. The slow waves were blocked by all of these alpha-adrenoceptor antagonists (10(-5) M), while the depolarizations were inhibited by yohimbine (greater than 10(-7) M) or phentolamine (10(-5) M), but not by nipradilol or prazosin (up to 10(-5) M). Contractions produced by exogenously applied noradrenaline (10(-6) M) were inhibited by the alpha-adrenoceptor antagonists; yohimbine or phentolamine (10(-6)-10(-5) M) showed complete inhibition and prazosin or nipradilol (up to 10(-5) M) partial inhibition. Contractions produced by high-potassium or current-stimulation were suppressed by high-concentrations (10(-6)-10(-5) M) of these alpha-adrenoceptor antagonists.(ABSTRACT TRUNCATED AT 250 WORDS)