Regional hemodynamic actions of selective corticotropin-releasing factor type 2 receptor ligands in conscious rats.
In conscious male Sprague-Dawley rats, we compared regional hemodynamic actions of the selective corticotropin-releasing factor type 2 (CRF(2)) receptor ligands human and mouse urocortin 2 (hUCN2 and mUCN2, respectively) with those of CRF. Bolus i.v. doses of 3 and 30 pmol kg(-1) hUCN2, mUCN2, or CRF had no significant hemodynamic actions, but at doses of 300 and 3000 pmol kg(-1), all three peptides caused dose-dependent tachycardia and hypotension, with rapid-onset, short-duration, mesenteric vasodilatation and slower-onset, more prolonged hindquarters vasodilatation but little or no change in renal vascular conductance. Pretreatment with the nonselective CRF receptor antagonist astressin or the selective CRF(2) receptor antagonist antisauvagine 30 abolished all the cardiovascular actions of all three peptides. Indomethacin had no effect on responses to hUCN2, and there was no evidence for any involvement of nitric oxide (NO) in the vasodilator actions of hUCN2. There was no evidence that recruitment of angiotensin- and endothelin-mediated vasoconstrictor mechanisms counteracted the vascular actions of hUCN2. The results indicate that the hemodynamic effects of i.v. hUCN2, mUCN2, and CRF depend on activation of CRF(2) receptors and do not involve NO or prostanoids.
Centre for Integrated Systems Biology and Medicine School of Biomedical Sciences, University of Nottingham NG7 2UH. UK. sheila.gardiner@nottingham.ac.uk
Sheila M
SM
Gardiner
Julie E
JE
March
Philip A
PA
Kemp
Anthony P
AP
Davenport
Katherine E
KE
Wiley
Terence
T
Bennett
D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology*; D004347:Drug Interactions; D006439:Hemodynamics / Q000187:drug effects*; D007189:Indans / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D019808:Losartan / Q000494:pharmacology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors* / Q000378:metabolism; D054832:Urocortins
D007189:Indans; D018019:Receptors, Corticotropin-Releasing Hormone; D054832:Urocortins; C518358:urocortin 2, mouse; C087551:1H-Indene-2-carboxylic acid, 1-(1,3-benzodioxol-5-yl)-3-(2- (carboxymethoxy)-4-methoxyphenyl)-2,3-dihydro-5-propoxy-, (1S,2R,3S)-; D003346:Corticotropin-Releasing Hormone; D019808:Losartan; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin