A novel model of conduit coronary constriction reveals local
actions of Endothelin-1 and Prostaglandin F2[alpha].
Rigel, Dean F., Suraj S. Shetty .
Research Department, Pharmaceuticals Division, Ciba-Geigy
Corporation, Summit, NJ 07901
APStracts 3:0478H, 1996.
We evaluated the effects of endothelin-1 (ET-1) and prostaglandin
F2[alpha] (PGF2[alpha]) selectively on conduit coronary artery
diameter using a novel approach in which the local concentration of
vasoactive agent was controlled and maintained in vivo. ET-1 and
PGF2[alpha] were applied topically (100 [mu]l every 3 min) to the
external surface of the left circumflex coronary artery (LCx) in
anesthetized dogs or to the bathing medium of isolated canine LCx
rings in parallel in vitro experiments. The dose-dependent
constrictions obtained in vivo and in vitro were similar with each
agent. Single, approximately maximally effective concentrations of
PGF2[alpha] evoked an initial rapid contraction followed by a slow
and sustained larger contraction in both preparations. In contrast,
single concentrations of ET-1 elicited a rapid constriction which
partially recovered (50-80%) in the ensuing 1.5-2 hours despite
continuous exposure to ET-1. After reversal of the ET-1 constriction,
PGF2[alpha] could still elicit a contraction, indicating a homologous
endothelin receptor desensitization. Both agents maximally decreased
conduit artery cross-sectional area in vivo by 40% without
significantly changing LCx resistance. Thus, this in situ technique
revealed effects of ET-1 and PGF2[alpha] on a localized segment of
coronary artery that were not discernible with either intravenous or
intracoronary administration.
Received 1 October 1996; accepted in final form 25 October 1996.
APS Manuscript Number H891-6.
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