Impairment of vascular function is associated with an age-related increase of lipid peroxidation in rats.
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 wk (n = 12) to 40 wk (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 the following. 1) An increase in sensitivity to alpha 1-adrenergic stimulation occurred between 20 and 40 wk of age. Cyclooxygenase inhibition decreased the sensitivity to phenylephrine only in the arteries from the 40-wk-old 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-wk-old rats than those from the 40-wk-old rats, indicating that nitric oxide modification of phenylephrine sensitivity decreased with age. 3) Endothelium-independent relaxations were not affected between 20 and 40 wk of age. 4) At 40 wk, the sensitivity to the methacholine-mediated relaxation response decreased without impairing the maximal relaxation response. This reduced sensitivity was removed with cyclooxygenase inhibition or thromboxane A2/prostaglandin H2 (PGH2) receptor blockade. 5) Aortas from the 40-wk-old 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 were due in part to a cyclooxygenase-dependent vasoconstrictor.
Davidge
S T
ST
Magee-Women Research Institute, Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh, Pennsylvania 15213, USA.
Hubel
C A
CA
McLaughlin
M K
MK
D000375:Aging / Q000378:metabolism*; D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D015153:Blotting, Western; D019086:Bridged Bicyclo Compounds, Heterocyclic; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005231:Fatty Acids, Unsaturated; D005260:Female; D006834:Hydrazines / Q000494:pharmacology; D008054:Lipid Peroxides / Q000378:metabolism*; D008469:Meclofenamic Acid / Q000494:pharmacology; D016210:Methacholine Chloride / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors; D010656:Phenylephrine / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects
D019086:Bridged Bicyclo Compounds, Heterocyclic; D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines; D008054:Lipid Peroxides; D014662:Vasoconstrictor Agents; D016210:Methacholine Chloride; D010656:Phenylephrine; D009569:Nitric Oxide; D008469:Meclofenamic Acid; C045749:SQ 29548; D011451:Prostaglandin-Endoperoxide Synthases; D019331:NG-Nitroarginine Methyl Ester