Effects of pH on contraction and Ca2+ mobilization in vascular smooth muscles of the rabbit basilar artery

The present study was undertaken to investigate the effects of extracellular pH (pH(a)) and intracellular pH (pH(i)) on 5-hydroxytryptamine (5-HT)-induced contraction and Ca2+ mobilization in vascular smooth muscles. Strip preparations of the rabbit basilar artery without endothelium were loaded with 40 mu M fura-2-AM and 2 mu M BCECF-AM and mounted in an organ bath. The isometric tension was recorded by using a force displacement transducer. Administration of 5-HT caused dose-dependent contraction in the rabbit basilar arteries. Acidification of pH(e) from 7.40 to 6.90 reduced the 5-HT-induced contraction and [Ca2+](i) transients. Alkalinization of pH(e) from 7.40 to 7.90, on the other hand, enhanced the contraction and elevation of [Ca2+](i). In the other series of experiments, pH(i) (7.12 in normal PSS) was selectively altered by adding either butyric acid or trimethylamine. Intracellular acidification (pH(i)=6.89) and alkalinization (pH(i)=7.35) without changes in pH(i) produced qualitatively similar effects to those caused by extracellular acidification and alkalinization, respectively. Ca-sensitivity, which is defined as Delta tension/Delta[Ca2+](i), was not affected by the alteration of pH(a) nor pH(i). In the Ca2+-free solution, the addition of 5-HT produced transient increases in [Ca2+](i) and isometric tension that were much smaller than those in the normal physiological salt solution. The 5-HT-induced responses of [Ca2+](i) and tension in the Ca2+-free solution were not affected by acidification nor alkalinization. These results suggest that a 5-HT-induced contraction is significantly modulated by pH through changing the [Ca2+](i) transients, and that the change of pH(i) plays, at least in part, a role in the alteration of 5-HT-induced contraction resulting from acidosis or alkalosis in the rabbit basilar artery.