Adenosine preconditions against endothelin-induced constriction of coronary arterioles.
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 microgram. 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 micrometer) 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 microM) for 20 min and 10 min of washout (n = 11). Blockade of A(2) receptors [8-(3-chlorostyryl)caffeine, 1 microM, n = 9] but not A(1) 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 A(2) receptor, against endothelin-induced constriction. This effect may offer a new protective function of adenosine in preventing excessive coronary constriction.
Merkus
D
D
Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA. dmerkus@mcw.edu
Stepp
D W
DW
Jones
D W
DW
Nishikawa
Y
Y
Chilian
W M
WM
D000241:Adenosine / Q000494:pharmacology*; D000818:Animals; D001160:Arterioles; D002110:Caffeine / Q000031:analogs & derivatives* / Q000494:pharmacology; D003326:Coronary Circulation / Q000187:drug effects* / Q000502:physiology*; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1; D066298:In Vitro Techniques; D019157:Ischemic Preconditioning, Myocardial; D008833:Microcirculation / Q000187:drug effects / Q000502:physiology; D058915:Purinergic P1 Receptor Antagonists; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology*; D014970:Xanthines / Q000494:pharmacology
D019332:Endothelin-1; D058915:Purinergic P1 Receptor Antagonists; D014665:Vasodilator Agents; D014970:Xanthines; C081320:8-(3-chlorostyryl)caffeine; D002110:Caffeine; C051360:1,3-dipropyl-8-cyclopentylxanthine; D000241:Adenosine