Grossini Elena, Molinari Claudio, Mary David A S G, Ghigo Ezio, Bona Gianni, Vacca Giovanni
Facoltà di Medicina e Chirurgia, Università del Piemonte Orientale "A. Avogadro," via Solaroli 17, I-28100 Novara, Italy.
Endocrinology. 2007 Feb;148(2):806-12. doi: 10.1210/en.2006-1230. Epub 2006 Nov 16.
The peptide ghrelin has been linked to the atherosclerotic process and coronary artery disease. We planned to study, for the first time, the primary effects of ghrelin on the intact coronary circulation and determine the mechanisms involved. In 24 sodium pentobarbitone-anesthetized pigs, changes in anterior descending coronary blood flow caused by intracoronary infusion of ghrelin at constant heart rate and arterial pressure were assessed using electromagnetic flowmeters. In 20 pigs, intracoronary infusion of ghrelin decreased coronary blood flow without affecting left ventricular maximum rate of change of left ventricular systolic pressure (dP/dt(max)), filling pressures of the heart or plasma levels of GH. In four pigs, this decrease was graded by step increments of infused dose of the hormone. The mechanisms of the above response were studied in the 20 pigs by repeating the experiment after coronary flow had returned to the control values observed before infusion. The ghrelin-induced coronary vasoconstriction was not affected by iv atropine (five pigs) or phentolamine (five pigs). This response was abolished by iv butoxamine (five pigs) and intracoronary N(omega)-nitro-l-arginine methyl ester (five pigs), even after reversing the increase in arterial pressure and coronary vascular resistance caused by the two blocking agents with iv infusion of papaverine. The present study showed that intracoronary infusion of ghrelin primarily caused coronary vasoconstriction. The mechanisms of this response were shown to involve the inhibition of a vasodilatory beta(2)-adrenergic receptor-mediated effect related to the release of nitric oxide.
胃饥饿素肽已被证明与动脉粥样硬化进程及冠状动脉疾病有关。我们计划首次研究胃饥饿素对完整冠状动脉循环的主要影响，并确定其中涉及的机制。在24只戊巴比妥钠麻醉的猪身上，使用电磁流量计评估在恒定心率和动脉压下冠状动脉内注入胃饥饿素所引起的前降支冠状动脉血流变化。在20只猪中，冠状动脉内注入胃饥饿素可使冠状动脉血流减少，而不影响左心室收缩压的最大变化率（dP/dt(max)）、心脏充盈压或生长激素的血浆水平。在4只猪中，这种减少随激素注入剂量的逐步增加而分级。在冠状动脉血流恢复到注入前观察到的对照值后，通过重复实验在这20只猪中研究上述反应的机制。胃饥饿素诱导的冠状动脉血管收缩不受静脉注射阿托品（5只猪）或酚妥拉明（5只猪）的影响。静脉注射丁氧胺（5只猪）和冠状动脉内注射N(ω)-硝基-L-精氨酸甲酯（5只猪）可消除这种反应，即使在用罂粟碱静脉输注逆转这两种阻断剂引起的动脉压和冠状动脉血管阻力增加之后。本研究表明，冠状动脉内注入胃饥饿素主要引起冠状动脉血管收缩。这种反应的机制表明涉及抑制与一氧化氮释放相关的血管舒张β₂-肾上腺素能受体介导的效应。
