Endogenous urocortins reduce vascular tone and renin–aldosterone/endothelin activity in experimental heart failure

• Published in: European heart journal 2005-10, Vol.26 (19), p.2046-2054
• Main Authors: Rademaker, Miriam T., Charles, Chris J., Espiner, Eric A., Frampton, Chris M., Lainchbury, John G., Richards, A. Mark
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Blood pressure; Cardiac Output, Low - metabolism; Cardiology. Vascular system; Corticotropin-Releasing Hormone - physiology; CRF(9–41); Endothelin; Endothelins - physiology; Female; Heart; Heart failure; Heart failure, cardiogenic pulmonary edema, cardiac enlargement; Hemodynamics - physiology; Medical sciences; Pacing; Random Allocation; Receptors, Corticotropin-Releasing Hormone - antagonists & inhibitors; Renin; Renin-Angiotensin System - physiology; Sheep; Urocortin; Urocortins
• ISSN: 0195-668X; 1522-9645
• DOI: 10.1093/eurheartj/ehi227

Aims To investigate the role of the endogenous urocortin peptides in heart failure (HF) through blockade of the corticotropin-releasing factor receptor 2 (CRF-R2). Methods and Results Eight sheep were administered the CRF-R2 antagonist CRF(9–41) (1.5 mg bolus) before (Normal) and after development of pacing-induced HF. Compared with controls, CRF(9–41) in HF significantly increased mean arterial pressure (MAP) (71±2 vs. 75±2 mmHg, P=0.0024) and calculated total peripheral resistance (CTPR) (33.3±5.2 vs. 39.4±5.9 mmHg/L/min, P=0.0455). Similar trends were observed in the Normal state (MAP 87±1 vs. 89±2 mmHg, P=0.0689; CTPR 21.9±2.0 vs. 24.4±2.4 mmHg/L/min, P=0.0731). Left atrial pressure was elevated similarly in both states (Normal P=0.0013; HF P=0.0298), whereas cardiac output tended to be reduced (Normal P=0.0614). CRF(9–41) increased plasma urocortin-I (Normal 10.3±0.8 vs. 19.8±1.3 pmol/L, P