Endogenous nitric oxide masks alpha 2-adrenergic coronary vasoconstriction during exercise in the ischemic heart.
Endogenous nitric oxide masks alpha 2-adrenergic coronary vasoconstriction during exercise in the ischemic heart.
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内源性一氧化氮掩盖了缺血性心脏运动期间的α2-肾上腺素能冠状血管收缩。
DOI：
10.1161/01.res.80.2.196
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发表时间：
1997
影响因子：
20.1
通讯作者：
Bache,RJ
中科院分区：
文献类型：
--
作者：
Ishibashi,Y;Duncker,DJ;Bache,RJ
以前，我们观察到α1-肾上腺素能血管收缩而非α2-肾上腺素能血管收缩限制了冠状动脉狭窄远端的血流，导致运动时心肌灌注不足。本研究旨在验证以下假设：运动时血管平滑肌α2-肾上腺素能血管收缩确实对冠状动脉狭窄远端产生血流限制作用，但该作用可被同时内皮α2-肾上腺素能刺激NO产生所抵消。8只犬在冠状动脉狭窄的情况下，在冠状动脉左前降支（LAD）内置入多普勒流速探头、液压封堵器和微导管，并在运动前和运动过程中输注α2肾上腺素能受体拮抗剂咪唑克生（1.0 μg·kg-1·min-1IC）。在对照期间和LNNA前后给予咪唑克生后，狭窄远端的冠状动脉压力保持恒定。无论是咪唑克生或LNNA改变任何全身血流动力学变量在休息或运动。在没有狭窄的情况下运动时，咪唑克生和LNNA对冠状动脉血流量没有影响。在存在使远端冠状动脉压力降至52±3 mm Hg的狭窄时，微球测量的平均心肌血流量在LAD依赖区为0.87±0.17 mL·min-1·g-1，在后对照区为2.52±0.30 mL·min-1·g-1。在远端冠状动脉压力没有变化的情况下，咪唑克生对LAD区域的平均心肌血流量没有影响（0.86±0.17 mL·min-1·g-1），但LNNA将平均心肌血流量降低至0.49±0.09（P<0.01）。然而，当在LNNA给药后出现冠状动脉狭窄的情况下在运动期间输注咪唑克生时，咪唑克生使平均心肌血流量增加至0.62±0.13 mL·min-1·g-1（P<0.01）。这些数据表明，α2-肾上腺素能刺激内皮NO的产生，这发生在运动过程中，在存在流量限制的冠状动脉狭窄，以抵消血管平滑肌α2-肾上腺素能血管收缩。
Previously, we observed that α1- but not α2-adrenergic vasoconstriction restricted blood flow distal to a coronary artery stenosis that resulted in myocardial hypoperfusion during exercise. This study was performed to test the hypothesis that vascular smooth muscle α2-adrenergic vasoconstriction during exercise does exert a flow-limiting effect distal to a coronary artery stenosis but that this action is counterbalanced by simultaneous endothelial α2-adrenergic stimulation of NO production. Eight dogs instrumented with a Doppler velocity probe, hydraulic occluder, and indwelling microcatheter in the left anterior descending coronary artery (LAD) were studied during treadmill exercise in the presence of a coronary artery stenosis before and during infusion of the α2-adrenergic receptor antagonist idazoxan (1.0 μg·kg−1·min−1IC) before and after NO synthase blockade withNG-monomethyl-l-arginine (LNNA, 1.5 mg/kg IC). Coronary pressure distal to the stenosis was maintained constant during the control period and after administration of idazoxan before and after LNNA. Neither idazoxan nor LNNA altered any of the systemic hemodynamic variables either at rest or during exercise. During exercise in the absence of a stenosis, idazoxan and LNNA had no effect on coronary blood flow. In the presence of a stenosis that decreased distal coronary pressure to 52±3 mm Hg, mean myocardial blood flow measured with microspheres was 0.87±0.17 mL·min−1·g−1in the LAD-dependent region and 2.52±0.30 mL·min−1·g−1in the posterior control region, respectively. With no change in distal coronary pressure, idazoxan had no effect on mean myocardial blood flow in the LAD region (0.86±0.17 mL·min−1·g−1), but LNNA decreased mean myocardial blood flow to 0.49±0.09 (P<.01). However, when idazoxan was infused during exercise in the presence of a coronary artery stenosis after LNNA administration, idazoxan increased mean myocardial blood flow to 0.62±0.13 mL·min−1·g−1(P<.01). These data demonstrate that α2-adrenergic stimulation of endothelial NO production, which occurs during exercise in the presence of a flow-limiting coronary artery stenosis, acts to counterbalance vascular smooth muscle α2-adrenergic vasoconstriction.