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 (pHi) 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. Also, Ca(2+)-free solution completely blocked the AVP-induced increase in [Na+]i. Moreover, Ca(2+)-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.
Okada
K
K
Department of Medicine, Jichi Medical School, Tochigi, Japan.
Ishikawa
S
S
Saito
T
T
D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism; D001127:Arginine Vasopressin / Q000031:analogs & derivatives / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D002478:Cells, Cultured; D003600:Cytosol / Q000378:metabolism; D003894:Deamino Arginine Vasopressin / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D011522:Protons; D051381:Rats; D011919:Rats, Inbred Strains; D017483:Receptors, Vasopressin; D012964:Sodium / Q000378:metabolism*
D057911:Angiotensin Receptor Antagonists; D011522:Protons; D017483:Receptors, Vasopressin; D001127:Arginine Vasopressin; C025043:vasopressin, 1-(1-mercaptocyclohexaneacetic acid)-2-(O- methyl-L-tyrosine)-8-L-arginine-; D012964:Sodium; D003894:Deamino Arginine Vasopressin; D002118:Calcium