Impairment of vascular function is associated with an age-related
increase of lipid peroxidation in the rat.
Davidge, Sandra T., Carl A. Hubel, and Margaret K. McLaughlin.
Magee-Womens Research Institute, Department of Obstetrics,
Gynecology and Reproductive Sciences, University of Pittsburgh,
Pittsburgh, PA 15213
APStracts 3:0221R, 1996.
We tested the hypothesis that an increase in endogenous lipid
peroxidation over time is associated with an impairment of
endothelium-dependent vascular function in resistance-sized
mesenteric arteries that is due in part to alterations of
arachidonate metabolism. Susceptibility to red blood cell hemolysis
and sera levels of malondialdehyde were increased (p<0.05) from
20 weeks (n=12) to 40 weeks (n=12) in female Sprague-Dawley rats.
Arteries were studied in a myograph by examining the endothelial
modification of phenylephrine vasoconstriction and the relaxation
responses of the mesenteric arteries to methacholine. We observed 1)
an increase in sensitivity to [alpha]1-adrenergic stimulation between
20 and 40 weeks of age. Cyclooxygenase inhibition decreased the
sensitivity to phenylephrine only in the arteries from the 40 week
rats indicating that a cyclooxygenase-dependent vasoconstrictor was
modifying the phenylephrine response. 2) Nitric oxide synthase
inhibition caused a greater increase in phenylephrine sensitivity in
the arteries from the 20 week rats than those from the 40 week rats
indicating that nitric oxide modification of phenylephrine
sensitivity decreased with age. 3) Endothelium-independent
relaxations were not affected between 20 and 40 weeks of age. 4) At
40 weeks, the sensitivity to the methacholine-mediated relaxation
response decreased without impairing the maximal relaxation response.
This reduced sensitivity was removed with cyclooxygenase inhibition
or TxA2/PGH2 receptor blockade. 5) Aortas from the 40 week rats had
an increased expression of PGH synthase. Collectively, these
observations indicate that in the female rat, an increase in lipid
peroxidation over time is associated with changes in endothelium
-dependent vascular function that was due in part to a cyclooxygenase
-dependent vasoconstrictor.
Received 11 September 1995; accepted in final form 14 May 1996.
APS Manuscript Number R577-5.
Article publication pending Am. J. Physiol. (Regulatory Integrative
Comp. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 28 June 96