Intravenous urocortin II decreases blood pressure through CRF(2) receptor in rats.
Urocortin II (Ucn II) is a new member of the corticotropin-releasing factor (CRF) family that binds selectively to the CRF subtype 2 receptor (CRF(2)). CRF or urocortin injected intravenously (i.v.) induced hypotension. We investigated the influence of iv human Ucn II (hUcn II) on basal mean blood pressure (MAP) and on the sympathetic mediated hypertensive response to TRH analog, RX-77368 injected intracisternally (i.c.) 20 min after hUcn II in urethane-anesthetized rats. Ucn II (3, 10, and 30 microg/kg, i.v.) significantly decreased basal MAP from baseline by -20.9+/-6.5, -21.3+/-5.4 and -46.8+/-6.5 mm Hg, respectively, after 10 min. RX-77368 (30 ng, i.c.) elevated MAP for over 90 min with a maximal hypertensive response at 20 min. Ucn II (3, 10, and 30 microg/kg, i.v.) did not alter the 20 min net rise in MAP induced by RX-77368 (35.7+/-7.1, 32.6+/-3.3 and 24.6+/-6.9 mm Hg, respectively) compared with vehicle (33.6+/-4.3 mm Hg). The selective CRF(2) antagonist, astressin(2)-B (60 microg/kg, i.v.) abolished hUcn II hypotensive action while having no effect on basal MAP. These data show that iv hUcn II induces hypotension through peripheral CRF(2) receptor while not altering the responsiveness to sympathetic nervous system-mediated rise in MAP.
Chen
Chih-Yen
CY
Department of Medicine and Brain Research Institute, University of California, Building 115 Room No 117, 11301 Wilshire Boulevard, Los Angeles, CA 90073, USA.
Doong
Ming-Luen
ML
Rivier
Jean E
JE
Taché
Yvette
Y
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D003346:Corticotropin-Releasing Hormone / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives; D051381:Rats; D017207:Rats, Sprague-Dawley; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013973:Thyrotropin-Releasing Hormone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D013997:Time Factors; D054832:Urocortins
C101531:CRF receptor type 2; D018019:Receptors, Corticotropin-Releasing Hormone; D054832:Urocortins; D013973:Thyrotropin-Releasing Hormone; C027979:L-pyroglutamyl-L-histidyl-3,3-dimethylprolinamide; D003346:Corticotropin-Releasing Hormone; D011761:Pyrrolidonecarboxylic Acid