MECHANISMS OF VASOPRESSIN-INDUCED INCREASE IN INTRACELLULAR NA+ IN VASCULAR SMOOTH-MUSCLE CELLS

The present study was undertaken to examine the interrelationship between the arginine vasopressin (AVP)-induced dynamic changes in intracellular Ca2+ and Na+ concentrations in cultured rat aortic vascular smooth muscle cells (VSMC) by the direct measurements of intracellular Na+ concentration ([Na+] i), cytosolic free calcium ([Ca2+]i), and intracellular pH (pH(i)) using fluorescence dyes. AVP increased [Ca2+]i and [Na+]i in a dose-dependent manner; the rise in [Ca2+]i preceded the rise in [Na+]i. Pretreatment with the V1 antagonist [1-(beta-mercapto-beta,beta-cyclopentamethylenepropionic acid) 2-(O-methyl)-tyrosine]AVP {[d(CH2)5Tyr(Me)]AVP} completely blocked the effects of AVP on [Ca2+]i and [Na+]i. The V2 agonist 1-desamino-8-D-AVP, DDAVP, did not affect basal [Na+]i or the AVP-induced increase in [Na+]i. Na+-free solution enhanced the AVP-induced mobilization of [Ca2+]i but abolished the AVP-induced increase in [Na+]i. Also, Ca2+-free solution completely blocked the AVP-induced increase in [Na+]i. Moreover, Ca2+-free solution decreased the AVP-induced intracellular acidification and blunted the later AVP-induced intracellular alkalinization. These results therefore indicate that after binding to the V1 receptor AVP increases [Na+]i mediated by the activation of Na+-Ca2+ and Na+-H+ exchanges in VSMC. All of these cellular events are completely dependent on an increase in cellular Ca2+ uptake produced by AVP.