Intracellular alkalinization augments α1-adrenoceptor-mediated vasoconstriction by promotion of Ca2+ entry through the non-L-type Ca2+ channels

Modulation by intracellular pH of the vasoconstriction induced by alpha -adrenoceptor agonists was investigated in isolated guinea pig aorta. NH4Cl (15 mM) increased intracellular pH of aortic smooth muscle cells by about 0.2 pH unit and significantly augmented KCl-induced contraction of aortic strips, whereas simultaneous administration of NH4Cl (15 mM) plus Na+ propionate (30 mM) failed to affect intracellular pH or contractility. NH4Cl (15 mM) potentiated contractions induced by alpha -adrenoceptor agonists, norepinephrine, phenylephrine and clonidine. Contraction induced by alpha (1)-selective adrenoceptor agonist, phenylephrine, but not that induced by norepinephrine or clonidine, was insensitive to inhibition by verapamil (1 muM). Phenylephrine-induced contraction was not affected by NH4Cl in Ca2+-free medium whereas extracellular Ca2+-induced contraction of phenylephrine-stimulated aorta was significantly augmented by NH4Cl. Consistently, Ca-45(2+) uptake into phenylephrine (1 muM)-stimulated aortic strips was increased by incubation with NH4Cl. The potentiating effects of NH4Cl on both phenylephrine-induced Ca2+ entry and contraction were antagonized by Na+ propionate. These results suggest that intracellular alkalinization facilitates alpha (1)-adrenoceptor-mediated vasoconstriction by facilitation of an agonist-induced Ca2+ entry pathway that is independent of L-type Ca2+ channels. (C) 2001 Elsevier Science B.V. All rights reserved.