Clinical Science (2007) 112, 485–491 (Printed in Great Britain) doi:10.1042/CS20060303 485 Urocortin 1 modulates the neurohumoral response to acute nitroprusside-induced hypotension in sheep Christopher J. CHARLES, Miriam T. RADEMAKER and A. Mark RICHARDS Christchurch Cardioendocrine Research Group, Christchurch School of Medicine and Health Sciences, PO Box 4345, Christchurch, New Zealand A B S T R A C T In addition to haemodynamic actions, Ucn1 (urocortin 1) has been reported to affect a number of hormonal systems; however, it remains unclear whether Ucn1 modulates circulating hormones under physiological conditions. Accordingly, in the present study, we have examined the effects of Ucn1 on haemodynamics, hormones and renal indices in normal conscious sheep subjected to a nitroprusside-induced hypotensive stimulus designed to alter hormonal levels within the physiological range. Ucn1 administration did not alter the haemodynamic response to nitroprus- side-induced hypotension. However, compared with the rise observed on the control day, plasma ANP (atrial natriuretic peptide; P = 0.043), BNP (brain natriuretic peptide; P = 0.038) and endothelin-1 (P = 0.011) levels were reduced following Ucn1 administration. Associated with this significant reduction in natriuretic peptides, the increase in urinary sodium output associated with rising pressures post-nitroprusside was abolished following Ucn1 administration (P = 0.048). Ucn1 had no significant effect on the response of hormones of the renin–angiotensin–aldosterone system or the hypothalamo–pituitary–adrenal axis. In conclusion, Ucn1, administered at physiologically relevant levels during nitroprusside-induced hypotension, attenuates the secretion/release of endothelin-1 and the cardiac natriuretic peptides ANP and BNP. Suppression of ANP and BNP probably led to an attenuated natriuretic response to recovery from acute hypotension. The threshold for the action of Ucn1 on the natriuretic peptides and endothelin-1 appears to be below that of other actions of Ucn1. INTRODUCTION Ucn1 (urocortin 1) is a 40-amino-acid peptide belonging to the CRF (corticotrophin-releasing factor) family. Ucn1 shares CRF-R2β (CRF-receptor 2β ) with CRF and is now emerging as a hormone potentially involved in the regulation of vascular tone and pressure/volume homo- eostasis [1]. A variety of biological actions have been demonstrated for Ucn1, including potent effects on the vasculature and heart. Haemodynamic actions of bolus administration of Ucn1 to normal sheep include dose-dependent increases in cardiac output, cardiac con- tractility and heart rate, with concurrent small increases in MAP (mean arterial pressure) [2,3]. Sheep with pacing- induced heart failure also had rises in cardiac output, but with small falls in MAP and major reductions in CTPR (calculated total peripheral resistance) and atrial pressures [3,4]. Key words: arterial pressure, atrial natriuretic peptide, brain natriuretic peptide, endothelin, haemodynamics, natriuresis, urocortin. Abbreviations: AngII, angiotensin II; ANP, atrial natriuretic peptide; AVP, arginine vasopressin; BNP, brain natriuretic peptide; CRF, corticotrophin-releasing factor; CTPR, calculated total peripheral resistance; ET-1, endothelin-1; HPA, hypothalamo–pituitary– adrenal; IV, intravenous; LSD, least squares difference; MAP, mean arterial pressure; PRA, plasma renin activity; RAAS, renin– angiotensin–aldosterone system; RAP, right atrial pressure; Ucn1, urocortin 1. Correspondence: Dr Christopher J. Charles (email chris.charles@chmeds.ac.nz). C  2007 The Biochemical Society