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


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Received for publication November 10, 2006.
Revised January 10, 2007.
Accepted for publication January 17, 2007.

A comparison between the cardiovascular actions of urocortin 1 and urocortin 2 (stresscopin related peptide) in conscious rats

Sheila Gardiner 1*, Julie March 1, Philip Kemp 1, Terence Bennett 1

1 University of Nottingham

* Address correspondence to: E-mail: sheila.gardiner{at}nottingham.ac.uk

Abstract

The aims of the study were, in conscious Sprague-Dawley rats, i) to compare the effects of stresscopin-related peptide (SRP) and urocortin 1 (UCN1) on blood pressure, heart rate and regional hemodynamics, ii) to determine whether or not there were residual tachycardic effects of SRP or UCN1 after cardiac autonomic blockade and iii) 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 3nmol kg-1 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. Pre-treatment 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. Pre-treatment 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 autonomically-mediated and likely to be largely reflex in origin. 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.


Key words: autonomic nervous system, hemodynamics, rats, urocortin 2, urocortin1, vasodilatation





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