Modulation of vascular smooth muscle sensitivity by preload and eicosanoid synthesis inhibition

J. T. Herlihy, A. Johns, M. J.K. Harper

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4 Scopus citations


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 μM), indomethacin (10 and 50 μg/ml), meclofenamate (50 and 100 μg/ml), 5,8,11,14-eicosatetraynoic acid (ETA, 50 and 100 μg/ml), and nordihydroguaiaretic acid (NDGA, 10 μM) 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 μM (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.

Original languageEnglish (US)
Pages (from-to)22/6
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Issue number6
StatePublished - 1987

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)


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