INFLUENCE OF BLOCKADE OF ALPHA(1)-ADRENOCEPTORS, BETA(1)-ADRENOCEPTORS AND VASOPRESSIN V-1A RECEPTORS ON THE CARDIOVASCULAR EFFECTS OF GAMMA(2)-MELANOCYTE-STIMULATING HORMONE (GAMMA(2)-MSH)

gamma(2)-Melanocyte-stimulating hormone (gamma(2)-MSH) and related mel anotropins have been shown to have various cardiovascular effects, inc luding acute, short-lasting increases in blood pressure (MAP) and hear t rate (HR). gamma(2)-MSH, administered intravenously, dose-dependentl y increased MAP and HR with an ED50 of approximately 30 nmol/kg and a maximal effect on MAP of approximately 55 mm Hg and on HR of around 70 beats per minute. Intravenous (i.v.) pretreatment with the alpha(1)-a drenoceptor antagonist, prazosin, caused the dose-response curve for t he effect of gamma(2)-MSH on MAP to shift to the right with a decrease in slope, whereas it had no effect on the dose-response curve for the effect on HR. I.v. pretreatment with the beta(1)-adrenoceptor antagon ist, metoprolol, had no effect on the dose-response curve for the effe ct of gamma(2)-MSH on MAP, but it caused the dose-response curve for t he effect of the peptide on HR to shift to the right with a decrease i n slope. Neither i.v. nor intracerebroventricular (i.c.v.) administrat ion of the vasopressin V-1A receptor antagonist, SR 49059 ((2S) 1-[(2R chlorophenyl)-1-(3,4-dimethoxy-benzene-sulfonyl)-3 -1H-indole-2-carbo nyl]-pyrrolidine-2-carboxamide), had significant effects on the dose-r esponse curves for the effects of the peptide on either MAP or HR. The doses of prazosin, metoprolol and SR 49059 were found to be effective in counteracting the effects of agonists for these receptors (phenyle phrine, isoprenaline and [Arg(8)]vasopressin, respectively). Taken tog ether, these results support the postulate that the effects of gamma(2 )-MSH are, at least partially, due to an increase in sympathetic outfl ow to the periphery (Gruber and Callahan (1989), Am J Physiol 257: R68 1-R694), and that this increase leads to increased activation of vascu lar alpha(1)-adrenoceptors and cardiac beta(1)-adrenoceptors. If, as w as suggested by these authors, gamma(2)-MSH acts via activation of a c entral vasopressin system, it is via a vasopressin receptor subtype ot her than the vasopressin V-1A receptor, since i.c.v. administration of a selective vasopressin V-1A receptor antagonist failed to interfere with the pressor and cardioaccelerator effects of gamma(2)-MSH.