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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. Adenosine-induced vasodilation was not inhibited by endothelial denudation, but [A.sub.2] receptor antagonism with 3,7-dimethyl-l-propargylxanthine and adenylate cyclase (AC) inhibition with SQ22536 significantly attenuated the dilation. In contrast, [A.sub.1] receptor antagonism with 8-cyclopentyl-l,3-dipropylxanthine significantly augmented the sensitivity to adenosine. Moreover, dilation to [A.sub.2a] receptor activation with 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadenosine hydrochloride was reduced by the [A.sub.1] receptor agonist (2S)-[N.sup.6]-(2-endo-norbornyl)adenosine. The nonspecific calcium-activated potassium ([K.sup.Ca]) channel blocker tetrabutylammonium attenuated adenosine-induced dilation, as did the intermediate-conductance [K.sub.Ca] blocker clotrimazole. Neither the large-conductance [K.sub.Ca] blocker iberiotoxin nor small-conductance [K.sub.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.sub.Ca] channels via an AC signaling pathway. The roles of [A.sub.1] and [A.sub.2] 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. receptors; potassium channels; microcirculation

We examined the influence of gender and climacteric status, two coronary risk factors, on bradykinin (BK)-induced dilation in adipose arterioles from men and women of different ages [premenopausal women (Pre-W), postmenopausal women (Post-W), and similar aged men (Y-M and O-M), respectively]. We examined the responses from both omental (more closely associated with coronary disease) and subcutaneous fat. Tissues were obtained at surgery and cannulated (60 mmHg) for measurement of internal diameter. In vessels from omental tissue, dilation to BK was more sensitive in Pre-W than other groups, whereas in vessels from subcutaneous tissue, sensitivity to BK was greater in both Pre-W and Post-W compared with Y-M and O-M. Maximal dilation was similar among groups. Indomethacin (Indo; [10.sup.-5] M) alone had no effect on dilation to BK in any groups, but Indo and [N.sup.[omega]]-nitro-L-arginine methyl ester (L-NAME; [10.sup.-4] M) reduced dilation to BK in Pre-W more than in Y-M. L-NAME increased dilation to BK in subcutaneous fat from Y-M but had no effect in Post-W and O-M. Indo- and L-NAME-resistant dilation in all vessels was markedly reduced by 30 mM KCl. There was no difference in sodium nitroprusside-induced dilation among groups. We conclude that gender and climacteric state contribute to mechanisms of microvascular regulation in humans. Functional vascular differences in visceral and subcutaneous fat may underlie the proposed differential influence of these tissues on cardiovascular risk. gender; bradykinin; human vessel; endothelium