HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 293/3/H1536    most recent 00377.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Rademaker, M. T. Articles by Richards, A. M. Search for Related Content PubMed PubMed Citation Articles by Rademaker, M. T. Articles by Richards, A. M.

Urocortin 1 administration from onset of rapid left ventricular pacing represses progression to overt heart failure

Christchurch Cardioendocrine Research Group, Department of Medicine, Christchurch School of Medicine, Christchurch, New Zealand

Submitted 26 March 2007 ; accepted in final form 23 May 2007

Urocortin 1 (Ucn1) may be involved in the pathophysiology of heart failure (HF), but the impact of Ucn1 administration on progression of the disease is unknown. The aim of this study was to investigate the effects of Ucn1 in sheep from the onset of cardiac overload and during the subsequent development of HF. Eight sheep underwent two 4-day periods of HF induction by rapid left ventricular pacing (225 beats/min) in conjunction with continuous infusions of Ucn1 (0.1 µg·kg^–1·h^–1 iv) and a vehicle control (0.9% saline). Compared with control, Ucn1 attenuated the pacing-induced decline in cardiac output (2.43 ± 0.46 vs. 3.70 ± 0.89 l/min on day 4, P < 0.01) and increases in left atrial pressure (24.9 ± 1.0 vs. 11.9 ± 1.1 mmHg, P < 0.001) and peripheral resistance (38.7 ± 9.4 vs. 25.2 ± 6.1 mmHg·l^–1·min, P < 0.001). Ucn1 wholly prevented increases in plasma renin activity (4.02 ± 1.17 vs. 0.87 ± 0.1 nmol·l^–1·h^–1, P < 0.001), aldosterone (1,313 ± 324 vs. 413 ± 174 pmol/l, P < 0.001), endothelin-1 (3.8 ± 0.5 vs. 2.0 ± 0.1 pmol/l, P < 0.001), and vasopressin (10.8 ± 4.1 vs. 1.8 ± 0.2 pmol/l, P < 0.05) during pacing alone and blunted the progressive increases in plasma epinephrine (2,132 ± 697 vs. 1,250 ± 264 pmol/l, P < 0.05), norepinephrine (3.61 ± 0.73 vs. 2.07 ± 0.52 nmol/l, P < 0.05), and atrial (P < 0.05) and brain (P < 0.01) natriuretic peptide levels. Ucn1 administration also maintained urine sodium excretion (0.75 ± 0.34 vs. 1.59 ± 0.50 mmol/h on day 4, P < 0.05) and suppressed pacing-induced declines in creatinine clearance (P < 0.05). These findings indicate that Ucn1 treatment from the onset of cardiac overload has the ability to repress the ensuing hemodynamic and renal deterioration and concomitant adverse neurohumoral activation, thereby delaying the development of overt HF. These data strongly support a use for Ucn1 as a therapeutic option early in the course of the disease.

cardiac output; hormones; renal function