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Characterization of the mechanism involved in the relaxant response of dopexamine in the guinea pig pulmonary artery in vitro.

Abstract
Dopexamine is a synthetic catecholamine used for the management of low-cardiac-output states. The purpose of this study was to characterize some of the mechanisms underlying dopexamine-mediated relaxation in the guinea pig pulmonary artery (PA) in vitro. Dopexamine (EC50, 1.2 microM; Rmax, 100%), like dobutamine (EC50, 1.4 microM, Rmax, 93.3%), prostacyclin (PGI2; EC50, 37 nM; Rmax, 96.2%), sodium nitroprusside (EC50, 370 pM; Rmax, 96.9%), forskolin (EC50, 47 pM: Rmax, 98.6%), and SKF 38393 (EC50, 120 nM; Rmax, 100%), caused graded relaxation in rings of PA precontracted by phenylephrine. The dopexamine vasorelaxation was antagonized by propranolol (1 microM), SCH 23390 (100 nM, a D1-dopamine antagonist), sulpiride (1 microM), glibenclamide (30 microM), tetraethylammonium (3 mM), apamin (100 nM), charybdotoxin (100 nM), SQ 22536 (10 microM, an adenylyl cyclase inhibitor), KT 5720 (10 microM, a protein kinase A inhibitor) and by calcitonin gene-related peptide (CGRP) or vasoactive intestinal peptide (VIP)-receptor antagonists (both 100 nM), as well as by chymotrypsin (1 U/ml). Neither the prior incubation of N(G)-nitro-L-arginine (100 pM), indomethacin (1 microM), nor removal of the vascular endothelium interfered with dopexamine vasorelaxation response in PA. Thus dopexamine relaxation in PA is mediated by activation of beta-adrenoceptors and dopamine receptors, and by the opening of both low- and high-conductance Ca2+-activated K+ channels, partially through adenosine triphosphate (ATP)-sensitive K+ channels. In addition, dopexamine-induced relaxation in PA seems to involve the release of peptides such as VIP and CGRP, an effect mediated by a cyclic adenosine monophosphate (cAMP)-dependent mechanism.
AuthorsT L Mazzuco, M A Dias, J B Calixto
JournalJournal of cardiovascular pharmacology (J Cardiovasc Pharmacol) Vol. 33 Issue 1 Pg. 86-92 (Jan 1999) ISSN: 0160-2446 [Print] United States
PMID9890401 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Adrenergic beta-Agonists
  • Dopamine Antagonists
  • Potassium Channel Blockers
  • dopexamine
  • Dopamine
Topics
  • Adrenergic beta-Agonists (pharmacology)
  • Animals
  • Dopamine (analogs & derivatives, pharmacology)
  • Dopamine Antagonists (pharmacology)
  • Dose-Response Relationship, Drug
  • Female
  • Guinea Pigs
  • In Vitro Techniques
  • Male
  • Potassium Channel Blockers
  • Pulmonary Artery (drug effects, physiology)
  • Vasodilation (drug effects)

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