Mechanism of vasodilation to adenosine in coronary arterioles from patients with heart disease
Open Access
- 1 April 2005
- journal article
- Published by American Physiological Society in American Journal of Physiology-Heart and Circulatory Physiology
- Vol. 288 (4), H1633-H1640
- https://doi.org/10.1152/ajpheart.00575.2004
Abstract
Adenosine is a key myocardial metabolite that elicits coronary vasodilation in a variety of pathophysiological conditions. We examined the mechanism of adenosine-induced vasodilation in coronary arterioles from patients with heart disease. Human coronary arterioles (HCAs) were dissected from pieces of the atrial appendage obtained at the time of cardiac surgery and cannulated for the measurement of internal diameter with videomicroscopy. Adenosine-induced vasodilation was not inhibited by endothelial denudation, but A2receptor antagonism with 3,7-dimethyl-1-propargylxanthine and adenylate cyclase (AC) inhibition with SQ22536 significantly attenuated the dilation. In contrast, A1receptor antagonism with 8-cyclopentyl-1,3-dipropylxanthine significantly augmented the sensitivity to adenosine. Moreover, dilation to A2areceptor activation with 2- p-(2-carboxyethyl)phenethylamino-5′- N-ethylcarboxamido-adenosine hydrochloride was reduced by the A1receptor agonist (2 S)- N6-(2-endo-norbornyl)adenosine. The nonspecific calcium-activated potassium (KCa) channel blocker tetrabutylammonium attenuated adenosine-induced dilation, as did the intermediate-conductance KCablocker clotrimazole. Neither the large-conductance KCablocker iberiotoxin nor small-conductance KCablocker apamin altered the dilation. In conclusion, adenosine endothelium independently dilates HCAs from patients with heart disease through a receptor-mediated mechanism that involves the activation of intermediate-conductance KCachannels via an AC signaling pathway. The roles of A1and A2receptor subtypes are opposing, with the former being inhibitory to AC-mediated dilator actions of the latter. These observations identify unique fundamental physiological characteristics of the human coronary circulation and may help to target the use of novel adenosine analogs for vasodilation in perfusion imaging or suggest new strategies for myocardial preconditioning.Keywords
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