| Abstract: | We tested thehypothesis that aging and insulin resistance interact to increasevascular dysfunction by comparing the function of isolated mesentericresistance arteries in obese, insulin-resistant JCR:LA-cp rats andlean, insulin-sensitive rats of the same strain at 3, 6, 9, and 12 moof age. The peak constrictor responses to norepinephrine,phenylephrine, and high potassium were elevated in arteries from obeserats. Responses to these agents increased with age in both obese andlean rats. An eicosanoid constrictor contributed substantially tovasoconstriction in the arteries from both lean and obese animals.Inhibition of nitric oxide synthase increased the vasoconstrictorresponse to norepinephrine in both obese and lean rats. This effectincreased with age in lean rats only. Vascular relaxation in responseto acetylcholine and sodium nitroprusside was impaired in the obeserats and did not alter with age. The results suggest that obeseJCR:LA-cp rats have enhanced maximal constriction, which originates inthe arterial smooth muscle and increases with age. There is evidencethat the ability of the arteries to compensate for the enhancedcontractility is impaired in obese rats, particularly with advanced age. |
