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Journal of Pharmacology And Experimental Therapeutics Fast Forward
First published on January 19, 2007; DOI: 10.1124/jpet.106.116962

0022-3565/07/3211-221-226$20.00
JPET 321:221-226, 2007
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CARDIOVASCULAR

A Comparison between the Cardiovascular Actions of Urocortin 1 and Urocortin 2 (Stresscopin-Related Peptide) in Conscious Rats

S. M. Gardiner, J. E. March, P. A. Kemp, and T. Bennett

Centre for Integrated Systems Biology and Medicine, School of Biomedical Sciences, University of Nottingham Medical School, Queen's Medical Centre, Nottingham, United Kingdom

The aims of the study were, in conscious Sprague-Dawley rats, to compare the effects of stresscopin-related peptide (SRP) and urocortin (UCN) 1 on blood pressure, heart rate, and regional hemodynamics; to determine whether or not there were residual tachycardic effects of SRP or UCN1 after cardiac autonomic blockade; and to investigate a possible involvement of corticotropin releasing factor type 1 (CRF1) receptor-mediated histamine release in the vasodilator actions of UCN1. SRP and UCN1 (both at 3 nmol/kg i.v.) caused hypotension, tachycardia, and mesenteric and hindquarters vasodilatation, but the magnitude and/or duration of the effects of UCN1 were generally greater than those of SRP. Pretreatment with atropine plus propranolol abolished the tachycardic effects of SRP and UCN1, and, under those conditions, the hypotensive effect of SRP, but not that of UCN1, was enhanced, probably because the hindquarters vasodilator effect of the latter was also reduced. Pretreatment with mepyramine plus cimetidine had no effect on the hemodynamic actions of either SRP or UCN1. It is concluded that, in conscious rats, the tachycardic effects of SRP and UCN1 are due to autonomic nervous activation mainly through baroreflex mechanisms. There is no evidence for an involvement of CRF1 receptor-mediated histamine release in the vasodilator actions of UCN1, but a propranolol-sensitive hindquarters vasodilator action of UCN, but not of SRP, was identified.

Received November 10, 2006; accepted January 17, 2007.

Address correspondence to: S. M. Gardiner, School of Biomedical Sciences, University of Nottingham Medical School, Queen's Medical Centre, Nottingham NG7 2UH, United Kingdom. E-mail: sheila.gardiner{at}nottingham.ac.uk






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