EFFECTS OF EXTRACELLULAR AND INTRACELLULAR PH ON VASCULAR ACTION OF ARGININE VASOPRESSIN

Compared with control studies performed at an extracellular pH (pH(e)) of 7.4, when vascular smooth muscle cells (VSMC) were preincubated in an acid extracellular medium (pH(e) 7.0) for 60 min the maximal arginine vasopressin (AVP)-induced sustained cellular contraction was reduced, whereas preincubation in an alkaline extracellular medium (pH(e) 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 pH(e) were parallelled by changes in pH(i), studies were performed in which only pH(i) 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 pH(e) may modulate the vascular responses to AVP by altering hormone receptor affinity, [Ca2+]i mobilization, and pH(i).