Antalarmin blockade of corticotropin releasing hormone-induced hypertension in rats.
Central administration of CRH results in endocrinological, cardiovascular, and behavioral effects that suggest stress or anxiety. Among these is a marked pressor response. Parenteral administration of CRH, however, results in hypotension. We used parenteral administration of antalarmin, a novel, small molecule CRH1 receptor antagonist, and alpha-helical CRH(9-41), a peptidic CRHR1/CRHR2 antagonist to attempt to determine the receptor mechanisms through which CRH is acting in both of these situations. Our results suggest that the hypertension produced by central CRH administration is mediated through central CRHR1 receptors, whereas the hypotension produced by parenteral CRH administration is mediated through peripheral CRHR2 receptors.
Briscoe
R J
RJ
Department of Pharmacology, University of Michigan, 48109, Ann Arbor, MI, USA.
Cabrera
C L
CL
Baird
T J
TJ
Rice
K C
KC
Woods
J H
JH
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology*; D006973:Hypertension / Q000139:chemically induced*; D008297:Male; D011743:Pyrimidines / Q000494:pharmacology*; D011758:Pyrroles / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors*
D011743:Pyrimidines; D011758:Pyrroles; D018019:Receptors, Corticotropin-Releasing Hormone; C103016:antalarmin; D003346:Corticotropin-Releasing Hormone