Intracellular alkalinization augments α 1-adrenoceptor-mediated vasoconstriction by promotion of Ca 2+ entry through the non-L-type Ca 2+ channels

Abstract

Modulation by intracellular pH of the vasoconstriction induced by α-adrenoceptor agonists was investigated in isolated guinea pig aorta. NH 4Cl (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 NH 4Cl (15 mM) plus Na + propionate (30 mM) failed to affect intracellular pH or contractility. NH 4Cl (15 mM) potentiated contractions induced by α-adrenoceptor agonists, norepinephrine, phenylephrine and clonidine. Contraction induced by α 1-selective adrenoceptor agonist, phenylephrine, but not that induced by norepinephrine or clonidine, was insensitive to inhibition by verapamil (1 μM). Phenylephrine-induced contraction was not affected by NH 4Cl in Ca 2+-free medium whereas extracellular Ca 2+-induced contraction of phenylephrine-stimulated aorta was significantly augmented by NH 4Cl. Consistently, 45Ca 2+uptake into phenylephrine (1 μM)-stimulated aortic strips was increased by incubation with NH 4Cl. The potentiating effects of NH 4Cl on both phenylephrine-induced Ca 2+ entry and contraction were antagonized by Na + propionate. These results suggest that intracellular alkalinization facilitates α 1-adrenoceptor-mediated vasoconstriction by facilitation of an agonist-induced Ca 2+ entry pathway that is independent of L-type Ca 2+ channels.