Effects of a selective agonist and antagonist of CRF2 receptors on cardiovascular function in the rat.
The aim of the present study was to investigate the effects of activation or blockade of the CRF(2) receptor subtype on cardiovascular function in conscious rats following systemic i.v. administration of the CRF(2) receptor peptide agonist urocortin 2 given alone and the selective CRF(2) receptor peptide antagonist antisauvagine-30 given alone. Urocortin 2 caused a dose-dependent reduction in mean arterial blood pressure and a dose-dependent increase in heart rate. Pretreatment with antisauvagine-30 blocked the hypotensive effect of urocortin 2. Antisauvagine-30 failed to produce any statistically significant effects on mean arterial blood pressure and heart rate at doses that completely blocked the effects of urocortin 2. These data verify the cardiovascular effects of selective CRF(2) receptor activation, but find no evidence for an endogenous CRF(2)-mediated tone.
Mackay
Kenneth B
KB
Neurocrine Biosciences Inc., 10555 Science Center Drive, San Diego, CA 92121-1102, USA. kmackay@neurocrine.com
Stiefel
Theodore H
TH
Ling
Nick
N
Foster
Alan C
AC
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D002320:Cardiovascular Physiological Phenomena / Q000187:drug effects; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects* / Q000502:physiology; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018019:Receptors, Corticotropin-Releasing Hormone / Q000819:agonists* / Q000037:antagonists & inhibitors* / Q000502:physiology; D054832:Urocortins
C101531:CRF receptor type 2; D010446:Peptide Fragments; D018019:Receptors, Corticotropin-Releasing Hormone; D054832:Urocortins; C116607:antisauvagine 30; D003346:Corticotropin-Releasing Hormone