Journal
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
Volume 288, Issue 4, Pages H1633-H1640Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpheart.00575.2004
Keywords
receptors; potassium channels; microcirculation
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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. Adenosineinduced vasodilation was not inhibited by endothelial denudation, but A(2) receptor antagonism with 3,7- dimethyl- 1- propargylxanthine and adenylate cyclase ( AC) inhibition with SQ22536 significantly attenuated the dilation. In contrast, A1 receptor antagonism with 8- cyclopentyl- 1,3- dipropylxanthine significantly augmented the sensitivity to adenosine. Moreover, dilation to A2a receptor activation with 2- p-( 2- carboxyethyl) phenethylamino- 5'- N- ethylcarboxamidoadenosine hydrochloride was reduced by the A1 receptor agonist ( 2S)- N-6-( 2- endo- norbornyl) adenosine. The nonspecific calcium- activated potassium ( K-Ca) channel blocker tetrabutylammonium attenuated adenosine- induced dilation, as did the intermediate- conductance K-Ca blocker clotrimazole. Neither the large- conductance K-Ca blocker iberiotoxin nor small- conductance K-Ca blocker 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 K-Ca channels via an AC signaling pathway. The roles of A1 and A2 receptor 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.
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