AJP - Heart and Circulatory Physiology, Vol 253, Issue 6 1492-H1498, Copyright © 1987 by American Physiological Society
Modulation of vascular smooth muscle sensitivity by preload and eicosanoid synthesis inhibition
J. T. Herlihy, A. Johns and M. J. Harper
Department of Physiology, University of Texas Health Science Center, San Antonio 78284.
An increase in preload from 0.75 to 10 g caused an increase in the
sensitivity of rabbit aortic strips to phenylephrine, serotonin, and KCl.
Several eicosanoid synthesis inhibitors were utilized to determine whether
production of endogenous eicosanoids contributed to the change in muscle
sensitivity. Quinacrine (10 microM), indomethacin (10 and 50
micrograms/ml), meclofenamate (50 and 100 micrograms/ml),
5,8,11,14-eicosatetraynoic acid (ETA, 50 and 100 micrograms/ml), and
nordihydroguaiaretic acid (NDGA, 10 microM) all shifted the
concentration-response curves of various agonists to the right, indicating
a decrease in the sensitivity of the muscle to these agents. Thromboxane
synthesis inhibition by 1 microM
(E)-3-[4-(1-imidazolylmethyl]phenyl-2-propenoate (OKY 046) exerted no
effect on sensitivity. Indomethacin at both concentrations caused a
parallel shift in the high and low preloaded strips but was unable to alter
the influence of preload on sensitivity. A similar effect was observed with
the lower concentrations of meclofenamate and ETA. NDGA and higher
concentrations of meclofenamate and ETA not only shifted the sensitivity in
both high and low preloaded strips but also eliminated the preload effect.
These results indicate that cyclooxygenase and lipoxygenase metabolites
both alter aortic smooth muscle sensitivity to contractile agents and
suggest that lipoxygenase metabolites may play a role in the change in
sensitivity seen with preload.
