Hori M, Kitakaze M, Tamai J, Koretsune Y, Iwai K, Iwakura K, Kagiya T, Kitabatake A, Inoue M, Kamada T
First Department of Medicine, Osaka University School of Medicine, Japan.
Am J Physiol. 1988 Aug;255(2 Pt 2):H250-60. doi: 10.1152/ajpheart.1988.255.2.H250.
To test the hypothesis that alpha 2-adrenoceptor activity exerts a dual control of coronary blood flow, i.e., vasoconstriction and augmentation of the vasodilatory effect of adenosine, four doses of adenosine were infused into left anterior descending coronary artery before and during alpha 2-adrenoceptor stimulation or attenuation in anesthetized open-chest dogs. During a moderate alpha 2-adrenoceptor attenuation (yohimbine or rauwolscine, ic), which did not alter coronary blood flow (CBF) at the base-line condition, the hyperemic response of CBF to infused adenosine was markedly reduced, whereas during the potent attenuation both base-line CBF and adenosine-induced hyperemic CBF were significantly increased. Inversely, the moderate alpha 2-stimulation (0.03 microgram.kg-1.min-1 norepinephrine with prazosin, ic, or 0.04 microgram.kg-1.min-1 clonidine ic, under propranolol pretreatment) augmented the adenosine-induced coronary vasodilation, but the potent alpha 2-stimulation (0.3 microgram.kg-1.min-1 norepinephrine with prazosin ic, or 0.3 microgram.kg-1.min-1 clonidine ic) reduced both base-line CBF hyperemic CBF. In contrast, alpha 2-adrenoceptor activity did not affect papaverine-induced coronary vasodilation. Moreover, the reactive hyperemic flow after a brief coronary occlusion was reduced significantly during the moderate alpha 2-adrenergic attenuation, but it was augmented during the potent one. These results indicate that the moderate activation of the alpha 2-adrenoceptor augments the hyperemic response of CBF to both exogenous and endogenous adenosine, whereas the potent alpha 2-activation may mask this vasodilatory effect through the coronary vasoconstrictive effect.
为了验证α2 -肾上腺素能受体活性对冠状动脉血流具有双重调控作用这一假说，即血管收缩以及增强腺苷的血管舒张作用，在麻醉开胸犬身上，于α2 -肾上腺素能受体刺激或减弱之前及期间，向左前降支冠状动脉内输注四剂腺苷。在中等程度的α2 -肾上腺素能受体减弱（育亨宾或萝芙木碱，静脉注射）时，基线状态下冠状动脉血流（CBF）未改变，但CBF对输注腺苷的充血反应显著降低，而在强效减弱时，基线CBF和腺苷诱导的充血性CBF均显著增加。相反，中等程度的α2 -刺激（在普萘洛尔预处理下，静脉注射0.03微克·千克-1·分钟-1去甲肾上腺素加哌唑嗪，或静脉注射0.04微克·千克-1·分钟-1可乐定）增强了腺苷诱导的冠状动脉舒张，但强效α2 -刺激（静脉注射0.3微克·千克-1·分钟-1去甲肾上腺素加哌唑嗪，或静脉注射0.3微克·千克-1·分钟-1可乐定）降低了基线CBF和充血性CBF。相比之下，α2 -肾上腺素能受体活性不影响罂粟碱诱导的冠状动脉舒张。此外，在中等程度的α2 -肾上腺素能减弱期间，短暂冠状动脉闭塞后的反应性充血血流显著减少，但在强效减弱时则增加。这些结果表明，α2 -肾上腺素能受体的中等程度激活增强了CBF对外源性和内源性腺苷的充血反应，而强效α2 -激活可能通过冠状动脉收缩作用掩盖这种血管舒张效应。
