Intravenous urocortin II decreases blood pressure through CRF2 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 (CRF2). CRF or urocortin injected intravenously (iv) 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 (ic) 20 min after hUcn II in urethane-anesthetized rats. Ucn II (3, 10, and 30 mug/kg, iv) significantly decreased basal MAP from baseline by - 20.9 +/- 6.5, - 21.3 +/- 5.4 and - 46.8 +/- 6.5 min Hg, respectively, after 10 min. RX-77368 (30 ng, ic) elevated MAP for over 90 min with a maximal hypertensive response at 20 min. Ucn II (3, 10, and 30 mug/kg, iv) 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 min Hg, respectively) compared with vehicle (33.6 +/- 4.3 min Hg). The selective CRF, antagonist, astressin(2)-B (60 mug/kg, iv) abolished hUcn II hypotensive action while having no effect on basal MAP. These data show that iv hUcn II induces hypotension through peripheral CRF2 receptor while not altering the responsiveness to sympathetic nervous system-mediated rise in MAP. (C) 2003 Elsevier Science B.V All rights reserved.