TY - JOUR T1 - Mechanism of action of vasopressin on prostaglandin synthesis and vascular function in the isolated rat kidney: effect of calcium antagonists and calmodulin inhibitors. JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 139 LP - 147 VL - 229 IS - 1 AU - C L Cooper AU - K U Malik Y1 - 1984/04/01 UR - http://jpet.aspetjournals.org/content/229/1/139.abstract N2 - We have investigated the mechanism of action of arginine vasopressin (AVP) on vascular tone and renal output of prostaglandins (PGs) by examining the effect of Ca++ depletion, Ca++ antagonists and calmodulin inhibitors in the isolated Tyrode perfused rat kidney. Administration of AVP (0.027-0.27 nmol) into the kidney produced a dose-related renal vasoconstriction and an increase in the output of PGE2 and 6-keto-PGF1 alpha, the stable hydrolysis product of PGI2. Omission of Ca++ (1.8 mM) or addition of Ca++ channel blockers, diltiazem (6.0 X 10(-5) M) or nimodipine (4.7 X 10(-5) M), to the perfusion fluid attenuated the renal vasoconstriction, but not the output of PGs elicited by AVP. Infusion of intracellular Ca++ antagonists, Dantrium (3.1 X 10(-5) M), TMB-8 (2.3 X 10(-6) M) or ryanodine (2 X 10(-6) M) or calmodulin inhibitors, trifluoperazine (2 X 10(-6) M) or W-7 (2 X 10(-6) M), abolished the rise in renal output of PGs produced by AVP during Ca++ depletion. Calmodulin inhibitors, which inhibited the AVP-induced release of PGs in the presence of Ca++, failed to alter the renal vasoconstrictor effect of the peptide. Administration of d(CH2)5Tyr(Me)AVP, a selective antagonist of pressor actions of AVP, abolished the renal vasoconstrictor response and release of PGs elicited by AVP. In contrast, d(CH2)5-D-ValVAVP, an antagonist of antidiuretic and to a lesser extent of pressor actions of AVP, failed to alter the renal vasoconstrictor response but attenuated the output of PGs produced by AVP. AVP antagonists did not alter the effect of angiotensin II (0.096 nmol) to cause renal vasoconstriction and enhance PG output.(ABSTRACT TRUNCATED AT 250 WORDS) ER -