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Am J Physiol Heart Circ Physiol 279: H2593-H2597, 2000;
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Vol. 279, Issue 6, H2593-H2597, December 2000

Adenosine preconditions against endothelin-induced constriction of coronary arterioles

Daphne Merkus, David W. Stepp, Deron W. Jones, Yasuhiro Nishikawa, and William M. Chilian

Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226

Myocardial hypoperfusion is accompanied by concomitant increases in adenosine and endothelin-1 (ET-1) production, but the vasodilatory effect of adenosine prevails over that of ET-1. Therefore, we hypothesized that adenosine-induced or ischemic preconditioning reduces the vasoconstrictive effect of ET-1. Coronary arteriolar diameter in vivo was measured using fluorescence microangiography in anesthetized open-thorax dogs. ET-1 (5 ng · kg-1 · min-1 administered intracoronary, n = 10) induced progressive constriction over 45 min [25 ± 6% (SE)]. The constriction was blocked by preconditioning with adenosine (25 µg · kg-1 · min-1 administered intracoronary) for 20 min and 10 min of washout (n = 10) or attenuated by ischemic preconditioning (four 5-min periods of ischemia, 9 ± 5% at 45 min). To investigate the receptor involved in this process, coronary arterioles (50-150 µm) were isolated and pressurized at 60 mmHg in vitro. The ET-1 dose-response curve (1 pM-5 nM) was rightward shifted after preconditioning with adenosine (1 µM) for 20 min and 10 min of washout (n = 11). Blockade of A2 receptors [8-(3-chlorostyryl)caffeine, 1 µM, n = 9] but not A1 receptors (8-cyclopentyl-1,3-dipropylxanthine, 100 nM, n = 7) prevented this shift. These results suggest that adenosine confers a vascular preconditioning effect, mediated via the A2 receptor, against endothelin-induced constriction. This effect may offer a new protective function of adenosine in preventing excessive coronary constriction.

coronary microcirculation; coronary blood flow; vasodilation; vasoconstriction; ischemic preconditioning


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