Characterization of the mechanism involved in the relaxant response of dopexamine in the guinea pig pulmonary artery in vitro.
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.
Mazzuco
T L
TL
Department of Pharmacology, Center of Biological Sciences, Universidade Federal de Santa Catarina, Florianopolis, Brazil.
Dias
M A
MA
Calixto
J B
JB
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D004298:Dopamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D026902:Potassium Channel Blockers; D011651:Pulmonary Artery / Q000187:drug effects* / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects*
D000318:Adrenergic beta-Agonists; D018492:Dopamine Antagonists; D026902:Potassium Channel Blockers; C046318:dopexamine; D004298:Dopamine