beta-Adrenergic regulation of constitutive nitric oxide synthase in cardiac myocytes
beta-Adrenergic regulation of constitutive nitric oxide synthase in cardiac myocytes
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DOI：
10.1152/ajpcell.1997.273.4.c1371
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发表时间：
1997-10-01
影响因子：
5.5
通讯作者：
Malinski, T
中科院分区：
文献类型：
--
作者：
Kanai, AJ;Mesaros, S;Malinski, T
一氧化氮（NO）参与心肌收缩力的内源性调控。然而，心肌细胞中NO的释放尚未得到证实。相应地，用定位在单个新生或成年大鼠心室肌细胞表面上的卟啉微传感器测量内源性NO产生（每个实验n > 6个新生和成年细胞）。在跳动的新生心肌细胞中，每次收缩时没有可检测到的自发NO释放。然而，去甲肾上腺素（NE; 0.25-1 μ M）引起搏动的新生儿（149 +/- 11至767 +/- 83 nM NO）和非收缩的成人（157 +/- 13至791 +/- 89 nM NO）细胞的瞬时NO释放。肾上腺素能激动剂释放的NO具有以下效力等级顺序：异丙肾上腺素（β（1）β（2））> NE（α/β（1））>多巴酚丁胺（β（1））近似肾上腺素（α/β（1）β（2））>叔丁烯（β（2））;苯肾上腺素（α）不释放NO。NE诱发的NO释放被N-G-单甲基-L-精氨酸、三氟拉嗪、鸟苷5 '-O-（2-硫代二磷酸）和硝苯地平可逆地阻断，但被3-异丁基-1-甲基黄嘌呤（0.5 mM = 14.5 +/- 1.6%）和BAY K 8644（10 μ M = 11.9 +/- 1%）增强。A-23187也释放了NO（10 μ M = 884 +/- 88 nM NO），鸟苷5 '-O-（3-硫代三磷酸）（1 μ M = 334 +/- 56 nM NO）和二丁酰腺苷3 '，5'-环一磷酸（10-100 μ M = 3 ',5 +/- 9至284 +/- 49 nM NO），但不受ATP、缓激肽、卡巴胆碱、8-溴鸟苷3'，5 '-环一磷酸或剪切应力的影响。这第一个功能演示心肌细胞中的组成型NO合酶表明其调节β-肾上腺素能信号通路，并可能提供一种新的机制，冠状动脉血管舒张和增强舒张舒张与肾上腺素能刺激观察。
Nitric oxide (NO) has been implicated in endogenous control of myocardial contractility. However, NO release has not yet been demonstrated in cardiac myocytes. Accordingly, endogenous NO production was measured with a porphyrinic microsensor positioned on the surface of individual neonatal or adult rat ventricular myocytes (n > 6 neonatal and adult cells per experiment). In beating neonatal myocytes, there was no detectable spontaneous NO release with each contraction. However, norepinephrine (NE; 0.25-1 mu M) elicited transient NO release from beating neonatal (149 +/- 11 to 767 +/- 83 nM NO) and noncontracting adult(157 +/- 13 to 791 +/- 89 nM NO) cells. NO was released by adrenergic agonists with the following rank order of potency: isoproterenol (beta(1) beta(2)) > NE (alpha/beta(1)) > dobutamine (beta(1)) approximate to epinephrine (alpha/beta(1) beta(2)) > tertbutylene (beta(2)); NO was not released by phenylephrine (alpha). NE-evoked NO release was reversibly blocked by N-G-monomethyl-L-arginine, trifluoperazine, guanosine 5'-O-(2-thiodiphosphate), and nifedipine but was enhanced by 3-isobutyl-1-methylxanthine (0.5 mM = 14.5 +/- 1.6%) and BAY K 8644 (10 mu M = 11.9 +/- 1%). NO was also released by A-23187 (10 mu M = 884 +/- 88 nM NO), guanosine 5'-O-(3-thiotriphosphate) (1 mu M = 334 +/- 56 nM NO), and dibutyryl adenosine 3',5'-cyclic monophosphate (10-100 mu M = 35 +/- 9 to 284 +/- 49 nM NO) but not by ATP, bradykinin, carbachol, 8-bromoguanosine 3',5'-cyclic monophosphate, or shear stress. This first functional demonstration of a constitutive NO synthase in cardiac myocytes suggests its regulation by a beta-adrenergic signaling pathway and may provide a novel mechanism for the coronary artery vasodilatation and enhanced diastolic relaxation observed with adrenergic stimulation.