Cardiac inotropic actions of urocortin in conscious sheep.
Parkes, David G., Joan Vaughan, Jean Rivier, Wylie Vale, and Clive N.
May.
Howard Florey Institute of Experimental Physiology and Medicine,
University of Melbourne, Parkville VIC 3052, Australia, and Peptide
Biology Laboratories, The Salk Institute, La Jolla, California
APStracts 3:0548H, 1996.
Urocortin (Ucn) is a recently isolated peptide related to the CRF
family, which can produce hemodynamic and hormonal actions in
conscious rats. This study examined in detail the cardiovascular
actions of Ucn and CRF following intravenous injection in chronically
instrumented, conscious sheep. Injection of Ucn produced dose
-dependent changes in cardiac contractility (aortic dF/dt, max. aortic
flow (Fmax)), mean arterial pressure (MAP), heart rate (HR), cardiac
output (CO) and coronary blood flow (CF). Ucn injected at 100[mu]g,
produced a potent increase in aortic dF/dt from 909+/-44 to a maximum
of 1849+/-90 l/min/sec, and Fmax from 25.5+/-0.8 to 36.6+/-1.4 l/min.
Cardiac contractility increased within 30min of injection, and
remained significantly elevated for up to 24hours. MAP increased from
78+/-2 to 90+/-3 mmHg, and HR increased from 73+/-4 to 103+/-9 b/min.
CO rose from 5.0+/-0.1 to 5.8+/-0.2 l/min, whereas central venous
pressure (CVP), total peripheral conductance (TPC) and stroke volume
(SV) were unchanged. All Ucn-induced cardiovascular effects were
inhibited by prior treatment with the CRF antagonist, [alpha]
-helicalCRF(9-41). Equimolar doses of CRF produced little change in
any hemodynamic parameter. Both peptides increased plasma levels of
ACTH and cortisol, with Ucn having a more potent effect than CRF. We
have shown for the first time that Ucn can produce potent and long
lasting actions to elevate cardiac contractility in conscious
animals.
Received 25 October 1996; accepted in final form 16 December
1996.
APS Manuscript Number H961-6.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 31 December 1996