Carperitide induces coronary vasodilation and limits infarct size in canine ischemic hearts: Role of NO.
Carperitide induces coronary vasodilation and limits infarct size in canine ischemic hearts: Role of NO.
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Carperitide 诱导冠状血管舒张并限制犬缺血性心脏的梗塞面积：NO 的作用。
DOI：
10.1038/hr.2014.70
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Takashima S,Kitakaze M.
中科院分区：
文献类型：
--
作者：
Asanuma H;Sanada S;Asakura M;Asano Y;Kim J;Shinozaki Y;Mori H;Minamino T;Takashima S,Kitakaze M.
卡必利是治疗心力衰竭的有效药物，因为它有利尿和血管扩张的作用。这种重组多肽还可能具有直接的心脏保护作用，因为卡珀肽降低了心力衰竭的严重程度，并限制了梗塞范围。由于冠状动脉血管扩张是一种重要的心脏保护治疗方式，我们研究了卡必利是否增加了犬心脏缺血时的冠脉血流量(CBF)，并改善了心肌代谢和收缩功能障碍。我们还测试了卡必利是否直接作用于限制梗塞范围。犬冠状动脉内注入卡必利0.025~0.2min g kg−1min−1。最小剂量为0.1μg kg−1min−1才能获得最大的血管扩张。为了测试卡培肽对缺血心脏的影响，我们降低了左冠状动脉前降支的灌流压，使CBF降至基线值的三分之一。静脉注射卡必利0.1μg kg−1min−1后10min，冠脉血中脑血流量、短轴缩短率(FS)和pH水平增加，心脏一氧化氮(NO)水平未见增加，这些变化可被心钠素受体拮抗剂HS-142-1或一氧化氮合酶抑制剂Lω-硝基精氨酸甲酯(NAME)拮抗。在缺血90分钟和随后的再灌流后，冠状动脉内环鸟苷一磷酸(GMP)水平升高，这也限制了心肌梗死的范围。这些影响又一次被L的名字削弱了。卡必利可增加脑血流量，减少心肌收缩和代谢功能障碍，并限制梗塞范围。此外，在卡必利诱导的血管扩张和心肌保护中，NO也是必需的。
Carperitide is effective for heart failure (HF) owing to its diuretic and vasodilatory effects. This recombinant peptide may also have direct cardioprotective effects because carperitide reduces the severity of heart failure and limits infarct size. Because coronary vasodilation is an important cardioprotective treatment modality, we investigated whether carperitide increased coronary blood flow (CBF) and improved myocardial metabolic and contractile dysfunction during ischemia in canine hearts. We also tested whether carperitide is directly responsible for limiting the infarct size. We infused carperitide at 0.025–0.2 μg kg− 1 min− 1 into the canine coronary artery. A minimum dose of 0.1 μg kg− 1 min− 1 was required to obtain maximal vasodilation. To test the effects of carperitide on ischemic hearts, we reduced perfusion pressure in the left anterior descending coronary artery such that CBF decreased to one-third of the baseline value. At 10 min after carperitide was infused at a dose of 0.1 μg kg− 1 min− 1, we observed increases in CBF, fractional shortening (FS) and pH levels in coronary venous blood without concomitant increases in cardiac nitric oxide (NO) levels; these changes were attenuated using either the atrial natriuretic peptide receptor antagonist HS-142-1 or the NO synthase inhibitor L ω-nitroarginine methyl ester (L-NAME). Cyclic guanosine monophosphate (GMP) levels in the coronary artery were elevated in response to carperitide that also limited the infarct size after 90 min of ischemia and subsequent reperfusion. Again, these effects were blunted by L-NAME. Carperitide increases CBF, reduces myocardial contractile and metabolic dysfunction and limits infarct size. In addition, NO is necessary for carperitide-induced vasodilation and cardioprotection in ischemic hearts.