Effects of arginine vasopressin in the heart are mediated by specific intravascular endothelial receptors

Arginine vasopressin induces vascular, inotropic and arrhythmogenic effects in the heart. Existing evidence, obtained indirectly, suggests that these effects occur through paracrine endothelial mechanisms. To demonstrate this , vasopressin was confined to the intravascular space by covalent coupling to high molecular weight (2 x 10(6) Da, vasopresin-dextran) dextran. Isolat ed guinea pig hearts were infused with equivalent concentrations of vasopre ssin and vasopressin-dextran. The negative inotropic and coronary vasopress or effects of vasopressin-dextran were similar to those evoked by vasopress in; in both cases effects were reversible. Free dextran had no effect on va scular resistance nor in ventricular developed pressure. The inotropic and vascular effects of both vasopressin and vasopressin-dextran were blocked b y the vasopressin receptor antagonist [Adamantaneacetyl(1), o-Et-D-Tyr(2), Val(4), Aminobutyryl(6), Arg(8,9)]vasopressin (Adam-vasopressin), indicatin g that the effects of the two agonists were vasopressin receptor-mediated. To elucidate possible endothelial intermediaries of these effects, isolated guinea pig hearts were infused simultaneously with vasopressin or vasopres sin-dextran and several inhibitors either of synthesis or blockers of recep tors of possible endothelial mediators. Only reactive blue 2, a P-2y purino ceptor antagonist, and suramin, a P-2y and a P-2x purinoceptor antagonist, caused a total reversal of vascular and inotropic effects of vasopressin an d vasopressin-dextran. Pyridoxalphosphate-6-Azophenyl-2'-4' disulphonic aci d, a P-2x purinoceptor antagonist, was without effect. Our results provide direct evidence that the short-term cardiac effects of vasopressin are due to selective activation of intravascular purinoceptors and suggest that an intermediary of these effects is ATP. (C) 2000 Elsevier Science B.V. All ri ghts reserved.