Urocortin 2 induces potent long-lasting inhibition of cardiac sympathetic drive despite baroreflex activation in conscious sheep
Urocortin 2 induces potent long-lasting inhibition of cardiac sympathetic drive despite baroreflex activation in conscious sheep
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DOI：
10.1677/joe-08-0505
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发表时间：
2010-02-01
影响因子：
4
通讯作者：
Richards, A. Mark
中科院分区：
文献类型：
--
作者：
Charles, Christopher J.;Jardine, David L.;Richards, A. Mark
新出现的证据表明，尿皮质素（UCN）肽有助于压力和容量调节，可能参与心血管疾病的病理生理。我们最近报道，静脉注射UCN 1有效地抑制心脏交感神经活动（CSNA）在正常绵羊。然而，关于UCN 2和交感神经系统之间可能的相互作用知之甚少。因此，我们研究了静脉注射UCN 2对CSNA，血流动力学和血浆中的正常清醒绵羊的儿茶酚胺的影响。静脉推注UCN 2（25和100 μ g）导致预期的血液动力学作用，包括动脉压的短暂福尔斯下降（P = 0.016）和心率（P < 0.001）和心输出量（P <0.001）的持续上升以及外周阻力的福尔斯下降（P < 0.001）。CSNA爆发频率呈双相反应（P < 0.001），急性上升，随后较长时间下降。CSNA爆发面积和发生率显示对UCN 2给药的反应延长，呈剂量依赖性福尔斯下降（均P < 0.001）。UCN 2还诱导血浆去甲肾上腺素水平的短暂升高（P = 0.006）。对UCN 2反应的心率显著升高在用六甲双铵进行药理学神经节阻滞的绵羊中得以保留。总之，这是第一项报告UCN 2对SNA的影响的研究，并表明尽管交感神经活动的普遍压力感受器诱导的激活，但对心脏的交感神经交通的有效抑制。这些发现表明UCN 2在心血管稳态中的重要作用，并保证进一步研究其在急性心肌损伤和心脏病中的潜在治疗应用。内分泌学杂志（2010）204，181-189
Emerging evidence suggests that the urocortin (UCN) peptides contribute to pressure and volume regulation with possible involvement in the pathophysiology of cardiovascular disease. We have recently reported that i.v. UCN1 potently inhibits cardiac sympathetic nerve activity (CSNA) in normal sheep. However, little is known about possible interactions between UCN2 and the sympathetic nervous system. Accordingly, we have examined the effects of i.v. UCN2 on CSNA, hemodynamics, and plasma catecholamines in normal conscious sheep. Bolus i.v. administration of UCN2 (25 and 100 mu g) resulted in the expected hemodynamic actions including transient falls in arterial pressure (P = 0.016) and more sustained rises in heart rate (P < 0.001) and cardiac output (P < 0.001) and falls in peripheral resistance (P < 0.001). CSNA burst frequency showed a biphasic response (P < 0.001) with an acute rise followed by a more prolonged fall. CSNA burst area and incidence showed prolonged, dose-dependent falls in response to UCN2 administration (all P < 0.001). UCN2 also induced a short-lived rise in plasma norepinephrine levels (P = 0.006). The marked rise in heart rate in response to UCN2 is preserved in sheep undergoing pharmacological ganglionic blockade with hexamethonium. In conclusion, this is the first study to report the effects of UCN2 on SNA and indicates potent inhibition of sympathetic traffic to the heart despite a generalized baroreceptor-induced activation of sympathetic activity. These findings suggest an important role for UCN2 in cardiovascular homeostasis and warrant further investigation for potential therapeutic applications in acute myocardial injury and heart disease. Journal of Endocrinology (2010) 204, 181-189