title: Influence of blockade of alpha 1-adrenoceptors, beta 1-adrenoceptors and vasopressin V1A receptors on the cardiovascular effects of gamma 2-melanocyte-stimulating hormone (gamma 2-MSH).
abstract: gamma 2-Melanocyte-stimulating hormone (gamma 2-MSH) and related melanotropins have been shown to have various cardiovascular effects, including acute, short-lasting increases in blood pressure (MAP) and heart rate (HR). gamma 2-MSH, administered intravenously, dose-dependently 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-adrenoceptor antagonist, prazosin, caused the dose-response curve for the 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 antagonist, metoprolol, had no effect on the dose-response curve for the effect of gamma 2-MSH on MAP, but it caused the dose-response curve for the effect of the peptide on HR to shift to the right with a decrease in slope. Neither i.v. nor intracerebroventricular (i.c.v.) administration of the vasopressin V1A receptor antagonist, SR 49059 ((2S) 1-[(2R 3S)-5-chloro-3-(2-chlorophenyl)-1-(3,4-dimethoxy-benzene-sulfonyl)- 3-hydroxy-2,3-dihydro-1H-indole-2-carbonyl]-pyrrolidine-2-carboxamide), had significant effects on the dose-response 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 (phenylephrine, isoprenaline and [Arg8]vasopressin, respectively). Taken together, these results support the postulate that the effects of gamma 2-MSH are, at least partially, due to an increase in sympathetic outflow to the periphery (Gruber and Callahan (1989), Am J Physiol 257: R681-R694), and that this increase leads to increased activation of vascular alpha 1-adrenoceptors and cardiac beta 1-adrenoceptors. If, as was suggested by these authors, gamma 2-MSH acts via activation of a central vasopressin system, it is via a vasopressin receptor subtype other than the vasopressin V1A receptor, since i.c.v. administration of a selective vasopressin V1A receptor antagonist failed to interfere with the pressor and cardioaccelerator effects of gamma 2-MSH.
authors.affiliation: Department of Medical Pharmacology, Rudolf Magnus Institute for Neurosciences, Utrecht University, The Netherlands.
authors.forename: P
authors.initials: P
authors.lastname: Van Bergen
authors.forename: T Y
authors.initials: TY
authors.lastname: De Winter
authors.forename: D J
authors.initials: DJ
authors.lastname: De Wildt
authors.forename: D H
authors.initials: DH
authors.lastname: Versteeg
mesh_terms: D058668:Adrenergic alpha-1 Receptor Antagonists; D058671:Adrenergic beta-1 Receptor Antagonists; D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D001794:Blood Pressure / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects*; D007211:Indoles / Q000494:pharmacology; D008297:Male; D009074:Melanocyte-Stimulating Hormones / Q000008:administration & dosage / Q000494:pharmacology*; D008790:Metoprolol / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D058671:Adrenergic beta-1 Receptor Antagonists; D065092:Antidiuretic Hormone Receptor Antagonists; D007211:Indoles; D011759:Pyrrolidines; D009074:Melanocyte-Stimulating Hormones; C082134:relcovaptan; D008790:Metoprolol; D011224:Prazosin