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.