Effects of extra- and intracellular pH on vascular action of arginine vasopressin.

Compared with control studies performed at an extra-cellular pH (pHe) of 7.4, when vascular smooth muscle cells (VSMC) were preincubated in an acid extracellular medium (pHe 7.0) for 60 min the maximal arginine vasopressin (AVP)-induced sustained cellular contraction was reduced, whereas preincubation in an alkaline extracellular medium (pHe 7.8) enhanced the vascular action of AVP. These changes in VSMC contraction were accompanied by a parallel decrease in AVP receptor affinity and cytosolic free calcium ([Ca2+]i) mobilization in the acid medium, increased AVP receptor affinity, and [Ca2+]i mobilization in alkaline medium. Because the changes in pHe were parallelled by changes in pHi, studies were performed in which only pHi was altered by administering the proton ionophore, carbonyl cyanide m-chlorophenylhydrazone (CCCP) (10(-6) M for 10 min). CCCP inhibited VSMC contraction in the absence of changes in AVP receptor binding and AVP-induced [Ca2+]i mobilization but abolished the AVP-induced cellular alkalinization. The results therefore indicate that in a nonbicarbonate buffer alterations in pHe may modulate the vascular responses to AVP by altering hormone receptor affinity, [Ca2+]i mobilization, and pHi.