Vascular wall dysfunction in JCR:LA-cp rats: effects of age and insulin resistance.
We tested the hypothesis that aging and insulin resistance interact to increase vascular dysfunction by comparing the function of isolated mesenteric resistance arteries in obese, insulin-resistant JCR:LA-cp rats and lean, insulin-sensitive rats of the same strain at 3, 6, 9, and 12 mo of age. The peak constrictor responses to norepinephrine, phenylephrine, and high potassium were elevated in arteries from obese rats. Responses to these agents increased with age in both obese and lean rats. An eicosanoid constrictor contributed substantially to vasoconstriction in the arteries from both lean and obese animals. Inhibition of nitric oxide synthase increased the vasoconstrictor response to norepinephrine in both obese and lean rats. This effect increased with age in lean rats only. Vascular relaxation in response to acetylcholine and sodium nitroprusside was impaired in the obese rats and did not alter with age. The results suggest that obese JCR:LA-cp rats have enhanced maximal constriction, which originates in the arterial smooth muscle and increases with age. There is evidence that the ability of the arteries to compensate for the enhanced contractility is impaired in obese rats, particularly with advanced age.
O'brien
S F
SF
Department of Surgery, University of Alberta, Edmonton, Alberta, Canada T6G 2S2.
Russell
J C
JC
Davidge
S T
ST
D000109:Acetylcholine / Q000494:pharmacology; D000375:Aging / Q000473:pathology*; D000818:Animals; D001161:Arteriosclerosis / Q000473:pathology / Q000503:physiopathology*; D001786:Blood Glucose; D001835:Body Weight; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015777:Eicosanoids / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008297:Male; D008469:Meclofenamic Acid / Q000494:pharmacology; D008638:Mesenteric Arteries / Q000473:pathology / Q000503:physiopathology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D009765:Obesity / Q000473:pathology / Q000503:physiopathology; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D011922:Rats, Mutant Strains; D014280:Triglycerides / Q000097:blood; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
D001786:Blood Glucose; D016861:Cyclooxygenase Inhibitors; D015777:Eicosanoids; D004791:Enzyme Inhibitors; D007328:Insulin; D014280:Triglycerides; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D009599:Nitroprusside; D010656:Phenylephrine; D009569:Nitric Oxide; D008469:Meclofenamic Acid; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine