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Beneficial hemodynamic, endocrine, and renal effects of urocortin in experimental heart failure

Comparison with normal sheep

Miriam T. Rademaker, PhD^*,*, Christopher J. Charles, PhD^*, Eric A. Espiner, MD, FRACP^*, Steve Fisher, NZCS, DipMLT^*, Christopher M. Frampton, PhD^*, Carl M. J. Kirkpatrick, Bpharm^*, John G. Lainchbury, MD, FRACP^*, M. Gary Nicholls, MD, FRACP, FACC^*, A. Mark Richards, MD, PhD, FRACP^* and Wylie W. Vale, PhD

^* Christchurch Cardioendocrine Research Group, Christchurch School of Medicine, Christchurch, New Zealand
Clayton Foundation Laboratories for Peptide Biology, The Salk Institute, La Jolla, California, USA

View larger version (37K): [in a new window]   Figure 1 Mean ± SEM hemodynamic responses to incremental boluses of urocortin and a vehicle control in eight normal sheep (left panel) and eight heart failure sheep (right panel). Baseline data points represent the mean of four samples taken in the hour preceding treatment. Significant differences (compared with time-matched control) are shown by: *p < 0.05; **p < 0.01; p < 0.001.

View larger version (34K): [in a new window]   Figure 2 Mean ± SEM plasma urocortin, arginine vasopressin, adrenocorticotrophic hormone (ACTH), and cortisol responses to incremental boluses of urocortin and a vehicle control in eight normal sheep (left panel) and eight heart failure sheep (right panel). Significant differences are shown by: *p < 0.05; **p < 0.01; p < 0.001.

View larger version (30K): [in a new window]   Figure 3 Mean ± SEM plasma renin activity, aldosterone, and endothelin-1 responses to incremental boluses of urocortin and a vehicle control in eight normal sheep (left panel) and eight heart failure sheep (right panel). Significant differences are shown by: *p < 0.05; **p < 0.01; p < 0.001.

View larger version (32K): [in a new window]   Figure 4 Mean ± SEM plasma atrial natriuretic peptide, brain natriuretic peptide, norepinephrine, and epinephrine responses to incremental boluses of urocortin and a vehicle control in eight normal sheep (left panel) and eight heart failure sheep (right panel). Significant differences are shown by: *p < 0.05; p < 0.001.

View larger version (55K): [in a new window]   Figure 5 Mean ± SEM urine volume, sodium, potassium, creatinine, and cyclic adenosine monophosphate (AMP) excretion in response to incremental boluses of urocortin (striped bars) and a vehicle control (open bars) in eight normal sheep (left panel) and eight heart failure sheep (right panel). The overnight sample was collected from 4:00 PM to 10:00 AM. Significant differences are shown by: *p < 0.05; **p < 0.01; p < 0.001.