Locatelli V, Rossoni G, Schweiger F, Torsello A, De Gennaro Colonna V, Bernareggi M, Deghenghi R, Müller E E, Berti F
Department of Pharmacology, University of Milan, Italy.
Endocrinology. 1999 Sep;140(9):4024-31. doi: 10.1210/endo.140.9.6948.
We previously reported that induction of selective GH deficiency in the rat exacerbates cardiac dysfunction induced by experimental ischemia and reperfusion performed on the explanted heart. In the same model, short-term treatment with hexarelin, a GH-releasing peptide, reverted this effect, as did GH. To ascertain whether hexarelin had non-GH-mediated protective effects on the heart, we compared hexarelin and GH treatment in hypophysectomized rats. Hexarelin (80 microg/kg sc), given for 7 days, prevented exacerbation of the ischemia-reperfusion damage induced by hypophysectomy. We also demonstrate that hexarelin prevents increases in left ventricular end diastolic pressure, coronary perfusion pressure, reactivity of the coronary vasculature to angiotensin II, and release of creatine kinase in the heart perfusate. Moreover, hexarelin prevents the fall in prostacyclin release and enhances recovery of contractility. Treatment with GH (400 microg/kg sc) produced similar results, whereas administration of EP 51389 (80 microg/kg sc), another GH-releasing peptide that does not bind to the heart, was ineffective. In conclusion, we demonstrate that hexarelin prevents cardiac damage after ischemia-reperfusion, and that its action is not mediated by GH but likely occurs through activation of specific cardiac receptors.
我们先前报道，诱导大鼠选择性生长激素缺乏会加重体外循环心脏实验性缺血再灌注所诱导的心脏功能障碍。在同一模型中，生长激素释放肽六肽素的短期治疗可逆转这种效应，生长激素也是如此。为确定六肽素对心脏是否具有非生长激素介导的保护作用，我们比较了六肽素和生长激素对垂体切除大鼠的治疗效果。给予六肽素（80微克/千克，皮下注射）7天，可预防垂体切除所诱导的缺血再灌注损伤的加重。我们还证明，六肽素可预防左心室舒张末期压力、冠状动脉灌注压力、冠状动脉血管对血管紧张素II反应性以及心脏灌注液中肌酸激酶释放的增加。此外，六肽素可预防前列环素释放的下降并增强收缩力的恢复。生长激素（400微克/千克，皮下注射）治疗产生了类似结果，而另一种不与心脏结合的生长激素释放肽EP 51389（80微克/千克，皮下注射）则无效。总之，我们证明六肽素可预防缺血再灌注后的心脏损伤，其作用并非由生长激素介导，而是可能通过激活特定的心脏受体发生。
