Inhibition of nitric oxide synthase augments myocardial contractile responses to beta-adrenergic stimulation.
Inhibition of nitric oxide synthase augments myocardial contractile responses to beta-adrenergic stimulation.
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一氧化氮合酶的抑制增强心肌对β-肾上腺素能刺激的收缩反应。
DOI：
10.1152/ajpheart.1996.271.6.h2646
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发表时间：
1996
期刊：
影响因子：
--
通讯作者：
Colucci,WS
中科院分区：
文献类型：
--
作者：
KeaneyJr,JF;Hare,JM;Balligand,JL;Loscalzo,J;Smith,TW;Colucci,WS
最近的体外证据表明一氧化氮（NO）在心肌收缩性调节中的作用。然而，一氧化氮在体内控制心功能中的具体作用尚不清楚。我们研究了NO合成酶（NOS）抑制对自主神经阻滞犬在β -肾上腺素能刺激下心肌收缩力的影响。冠脉内灌注特异性NOS抑制剂ng -硝基- l -精氨酸甲酯（L-NAME）前后分别灌注多巴酚丁胺（1 ~ 50微克/分钟）和异丙肾上腺素（0.1、0.5微克/分钟）。冠状动脉内多巴酚丁胺导致峰值压力一阶导数（dP/dtmax）的剂量依赖性增加，最大可达195±10% （P < 0.001）。冠脉内L-NAME以0.1和1 mg/min的速率抑制NOS后，多巴酚丁胺对dP/dtmax的反应显著增强，分别增加276 +/- 17和317 +/- 26% （P < 0.001）。冠状动脉内异丙肾上腺素可使dP/dtmax最大增加116 +/- 15% (P < 0.001)，在以0.1和1 mg/min L-NAME抑制NOS后，dP/dtmax分别增加154 +/- 17和157 +/- 18% （P < 0.002）。L-NAME对基线dP/dtmax没有影响，但确实降低了心肌鸟苷3′，5′-环单磷酸含量。这些结果提示一氧化氮在体内对β -肾上腺素能刺激反应的心肌收缩性控制中的作用。
Recent in vitro evidence suggests a role for nitric oxide (NO) in the modulation of myocardial contractility. The specific role of NO in the control of cardiac function in vivo, however, remains unclear. We investigated the effect of NO synthase (NOS) inhibition on myocardial contractility in response to beta-adrenergic stimulation in autonomically blocked dogs. Intracoronary infusions of dobutamine (1-50 micrograms/min) and isoproterenol (0.1 and 0.5 microgram/min) were performed before and after the intracoronary administration of the specific NOS inhibitor NG-nitro-L-arginine methyl ester (L-NAME). Intracoronary dobutamine resulted in a dose-dependent increase in peak first derivative of pressure (dP/dtmax) to a maximum of 195 +/- 10% (P < 0.001). After inhibition of NOS with intracoronary L-NAME at rates of 0.1 and 1 mg/min, the response to dobutamine was significantly enhanced with dP/dtmax, increasing 276 +/- 17 and 317 +/- 26%, respectively (P < 0.001). Intracoronary isoproterenol resulted in a maximum increase in dP/dtmax of 116 +/- 15% (P < 0.001) that further increased to 154 +/- 17 and 157 +/- 18% after NOS inhibition with 0.1 and 1 mg/min L-NAME, respectively (both P < 0.002). L-NAME had no effect on baseline dP/dtmax but did produce a reduction in myocardial guanosine 3',5'-cyclic monophosphate content. These results suggest a role for NO in the control of myocardial contractility in response to beta-adrenergic stimulation in vivo.