Modulation of vascular smooth muscle sensitivity by preload and eicosanoid synthesis inhibition.
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.
Department of Physiology, University of Texas Health Science Center, San Antonio 78284.
J T
JT
Herlihy
A
A
Johns
M J
MJ
Harper
D015117:5,8,11,14-Eicosatetraynoic Acid / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004537:Eicosanoic Acids / Q000096:biosynthesis*; D005260:Female; D007213:Indomethacin / Q000494:pharmacology; D009637:Masoprocol / Q000494:pharmacology; D008469:Meclofenamic Acid / Q000494:pharmacology; D008689:Methacrylates / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D010656:Phenylephrine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D011796:Quinacrine / Q000494:pharmacology; D011817:Rabbits; D012701:Serotonin / Q000494:pharmacology
D004537:Eicosanoic Acids; D008689:Methacrylates; D015117:5,8,11,14-Eicosatetraynoic Acid; D010656:Phenylephrine; D012701:Serotonin; D008469:Meclofenamic Acid; D011189:Potassium Chloride; D009637:Masoprocol; D011796:Quinacrine; C034364:ozagrel; D007213:Indomethacin