Christchurch Heart Institute, Department of Medicine, University of Otago-Christchurch, Christchurch, New Zealand.
Circ Heart Fail. 2013 Jul;6(4):825-32. doi: 10.1161/CIRCHEARTFAILURE.112.000205. Epub 2013 Jun 10.
Mineralocorticoid receptor antagonists (MRAs) have become established therapy in heart failure (HF). Urocortin 2 (Ucn2) is a novel peptide with potential in the treatment of this disease. The present study investigated the interactions of acute administration of Ucn2 and an MRA in experimental HF.
Ucn2 and an MRA (canrenoic acid [CA]) were infused for 4 hours, both singly and together, in 8 sheeps with pacing-induced HF. Ucn2, when administered as an adjunct to CA, further improved hemodynamic indices relative to that achieved by CA alone, producing additional increases in cardiac output and decreases in left atrial pressure and peripheral resistance but without eliciting a supplementary reduction in arterial pressure. Ucn2 cotreatment reversed CA-induced rises in circulating aldosterone levels, and also significantly reduced plasma renin activity, angiotensin II, and vasopressin concentrations. Although both CA and Ucn2 infusion produced a diuresis and natriuresis, responses with Ucn2 and Ucn+CA were 2- to 3-fold greater than that elicited by separate CA. Ucn2 cotherapy additionally increased urine potassium and creatinine excretion. In contrast to the rise in plasma potassium induced by CA, Ucn2 cotreatment reduced potassium concentrations.
Ucn2 cotreatment with an MRA in HF further improved hemodynamics relative to that achieved by CA alone, while also reducing plasma renin activity, angiotensin II, aldosterone and vasopressin levels, and enhancing renal function. Importantly, Ucn2 prevented CA-induced rises in plasma potassium. These data demonstrate a favorable profile of effects with short-term adjunct Ucn2 therapy and an MRA in HF.
醛固酮受体拮抗剂（MRAs）已成为心力衰竭（HF）的标准治疗方法。脑尿钠肽 2（Ucn2）是一种新型肽类物质，具有治疗这种疾病的潜力。本研究探讨了急性给予 Ucn2 和 MRA 在实验性 HF 中的相互作用。
在 8 只起搏诱导 HF 的绵羊中，Ucn2 和 MRA（卡奈诺酸[CA]）分别单独和联合输注 4 小时。与 CA 单独给药相比，Ucn2 作为 CA 的辅助药物，进一步改善了血液动力学指标，增加了心输出量，降低了左心房压力和外周阻力，但没有引起动脉压的额外降低。Ucn2 联合治疗逆转了 CA 诱导的循环醛固酮水平升高，还显著降低了血浆肾素活性、血管紧张素 II 和血管加压素浓度。尽管 CA 和 Ucn2 输注都产生了利尿和排钠作用，但 Ucn2 和 Ucn+CA 的反应比单独 CA 引起的反应高 2-3 倍。Ucn2 联合治疗还增加了尿钾和肌酐的排泄。与 CA 引起的血浆钾升高相反，Ucn2 联合治疗降低了钾浓度。
HF 中 Ucn2 与 MRA 联合治疗较 CA 单独治疗进一步改善了血液动力学，同时降低了血浆肾素活性、血管紧张素 II、醛固酮和血管加压素水平，增强了肾功能。重要的是，Ucn2 防止了 CA 引起的血浆钾升高。这些数据表明，HF 中短期 Ucn2 联合 MRA 治疗具有良好的效果。
