Wright R S, Wei C M, Kim C H, Kinoshita M, Matsuda Y, Aarhus L L, Burnett J C, Miller W L
Department of Medicine, Mayo Clinic, Rochester, Minnesota 55905, USA.
J Am Coll Cardiol. 1996 Oct;28(4):1031-8. doi: 10.1016/s0735-1097(96)00241-0.
We tested the hypothesis that C-type natriuretic peptide (CNP) mediates coronary vasodilation through activation of cyclic guanosine monophosphate (cGMP) by way of particulate guanylate cyclase.
CNP has known peripheral vasodilator properties, and preliminary data have suggested that it can function as a coronary vasodilator.
The actions of CNP were studied in instrumented dogs and in organ chamber rings in the presence and absence of a known antagonist to particulate guanylate cyclase, HS-142-1. Additionally, the actions of HS-142-1 were tested on acetylcholine-mediated coronary vasodilation, and immunohistochemical staining was utilized to localize the presence of CNP in the coronary endothelium.
CNP relaxed isolated coronary arteries with (mean +/- SEM 45.9 +/- 7%) and without (72.0 +/- 7%) an endothelium (p < 0.05 for CNP effect alone, p < 0.05 for endothelium vs. no endothelium with CNP). Intracoronary infusions increased coronary blood flow (baseline, 64.6 +/- 5.1 ml/min; CNP-5, 79.9 +/- 6.1; CNP-20, 103.3 +/- 13.6* [p < 0.05 vs. baseline value]) and reduced coronary vascular resistance (baseline, 1.6 +/- 0.3 mm Hg/ml per min; CNP-5, 1.4 +/- 0.3; CNP-20, 1.2 +/- 0.3*). Intracoronary injections increased coronary blood flow (delta baseline coronary flow, 30 +/- 9* ml/min [p < 0.05]). HS-142-1 significantly attenuated these increases (delta coronary flow, 30 +/- 9 ml/min [CNP] to 14 +/- 6 [CNP + HS-142-1] [p < 0.05 CNP vs. CNP + HS-142-1]) and the relaxation of organ chamber rings (56 +/- 7% [CNP] to 18 +/- 6% [HS-142-1 + CNP]). Finally, CNP was localized to the coronary endothelium and smooth muscle by immunohistochemical staining.
CNP functions as a coronary vasodilator through activation of cGMP by way of particulate guanylate cyclase. CNP-mediated coronary vasodilation is attenuated by intracoronary HS-142-1. Intracoronary HS-142-1 does not affect acetylcholine-mediated coronary vasodilation. These observations support a role for exogenous CNP as a potent coronary vasodilator.
我们验证了如下假设，即C型利钠肽（CNP）通过颗粒型鸟苷酸环化酶激活环磷酸鸟苷（cGMP）来介导冠状动脉舒张。
已知CNP具有外周血管舒张特性，且初步数据表明它可作为冠状动脉舒张剂发挥作用。
在有或没有颗粒型鸟苷酸环化酶已知拮抗剂HS-142-1存在的情况下，对植入仪器的犬以及器官浴槽中的血管环进行CNP作用的研究。此外，测试了HS-142-1对乙酰胆碱介导的冠状动脉舒张的作用，并利用免疫组织化学染色来定位冠状动脉内皮中CNP的存在。
CNP使有内皮（平均±标准误45.9±7%）和无内皮（72.0±7%）的离体冠状动脉舒张（单独使用CNP时p<0.05，使用CNP时内皮组与无内皮组相比p<0.05）。冠状动脉内输注增加了冠状动脉血流量（基线值，64.6±5.1ml/min；CNP-5，79.9±6.1；CNP-20，103.3±13.6*[与基线值相比p<0.05]）并降低了冠状动脉血管阻力（基线值，1.6±0.3mmHg/ml每分钟；CNP-5，1.4±0.3；CNP-20，1.2±0.3*）。冠状动脉内注射增加了冠状动脉血流量（冠状动脉血流基线变化量，30±9*ml/min[p<0.05]）。HS-142-1显著减弱了这些增加（冠状动脉血流变化量，[CNP时]30±9ml/min至[CNP+HS-142-1时]14±6[CNP与CNP+HS-142-1相比p<0.05]）以及器官浴槽血管环的舒张（[CNP时]56±7%至[HS-142-1+CNP时]18±6%）。最后，通过免疫组织化学染色将CNP定位到冠状动脉内皮和平滑肌。
CNP通过颗粒型鸟苷酸环化酶激活cGMP来作为冠状动脉舒张剂发挥作用。冠状动脉内注射HS-142-1可减弱CNP介导的冠状动脉舒张。冠状动脉内注射HS-142-1不影响乙酰胆碱介导的冠状动脉舒张。这些观察结果支持外源性CNP作为一种强效冠状动脉舒张剂的作用。
