McRaven D R, Mark A L, Abboud F M, Mayer H E
J Clin Invest. 1971 Apr;50(4):773-8. doi: 10.1172/JCI106548.
Coronary responses to adrenergic stimuli were determined in the intact beating heart before and after administration of practolol, 4-(2-hydroxy-3-isopropylaminoproproxy) acetanilide, which in low doses blocks myocardial but not vascular beta receptors. The left circumflex coronary artery of dogs was perfused with arterial blood at constant flow, and coronary perfusion pressure was measured. Before practolol, intracoronary injections of isoproterenol and norepinephrine and electrical stimulation of left cardiac sympathetic nerves caused reductions in perfusion pressure or vasodilatation associated with increases in left ventricular dp/dt, heart rate, and systolic pressure. After practolol, the coronary vasodilator response to isoproterenol was reduced by about 30% and occurred without significant changes in dp/dt, heart rate, and pressures. The addition of propranolol blocked completely the coronary responses to isoproterenol. Vascular responses to isoproterenol in the paw were not altered by practolol. Practolol antagonized the increases in dp/dt, heart rate, and systolic pressure and reversed coronary responses to norepinephrine and nerve stimulation from dilatation to constriction. The constriction, in turn, was reduced or reversed by phentolamine, an alpha receptor antagonist. Propranolol did not augment the constriction seen in response to norepinephrine and nerve stimulation after practolol. These results indicate that the coronary vasodilator action of norepinephrine and sympathetic nerve stimulation is indirect and caused by stimulation of myocardial beta receptors. The direct effect of these two stimuli on coronary vessels is minimal and is mediated through stimulation of alpha (vasoconstrictor) receptors. In contrast, the coronary vasodilator response to isoproterenol is both direct and indirect, resulting from stimulation of vascular and myocardial beta receptors; the direct vascular effect predominated in this study.
在完整的跳动心脏中，于给予心得宁（4-(2-羟基-3-异丙氨基丙氧基)乙酰苯胺）前后，测定对肾上腺素能刺激的冠状动脉反应。心得宁小剂量时可阻断心肌而非血管的β受体。以恒定流量用动脉血灌注犬的左旋冠状动脉，并测量冠状动脉灌注压。在给予心得宁之前，冠状动脉内注射异丙肾上腺素和去甲肾上腺素以及电刺激左心交感神经会导致灌注压降低或血管舒张，同时伴有左心室dp/dt、心率和收缩压升高。给予心得宁后，对异丙肾上腺素的冠状动脉舒张反应降低约30%，且在dp/dt、心率和血压无显著变化的情况下发生。加入普萘洛尔可完全阻断对异丙肾上腺素的冠状动脉反应。心得宁未改变爪部对异丙肾上腺素的血管反应。心得宁拮抗dp/dt、心率和收缩压的升高，并使对去甲肾上腺素和神经刺激的冠状动脉反应从舒张转变为收缩。反过来，这种收缩可被α受体拮抗剂酚妥拉明减弱或逆转。普萘洛尔并未增强心得宁后对去甲肾上腺素和神经刺激所见的收缩。这些结果表明，去甲肾上腺素和交感神经刺激的冠状动脉舒张作用是间接的，由心肌β受体刺激引起。这两种刺激对冠状动脉血管的直接作用极小，且通过α（血管收缩）受体刺激介导。相比之下，对异丙肾上腺素的冠状动脉舒张反应既是直接的也是间接的，由血管和心肌β受体刺激所致；在本研究中直接血管效应占主导。
