DEFECTIVE ENDOTHELIUM-DEPENDENT RELAXATION IN THE JCR-LA-CORPULENT RAT

Endothelium-dependent relaxation of the aorta was assessed in JCR:LA-c orpulent rats, which are hyperphagous, hyperlipidemic, hyperinsulinemi c, and obese and spontaneously develop atherosclerotic disease and myo cardial lesions. The findings in corpulent rats (6 months of age) were compared with those in age- and sex-matched lean rats. Aortic rings w ere prepared and mounted in Krebs-Henseleit buffer in a conventional o rgan bath. The tissue was contracted with norepinephrine (10(-6) mol/L ), and relaxation was induced using acetylcholine, the calcium ionopho re A23187, or bradykinin. The maximum relaxation to acetylcholine was impaired in corpulent male rats compared with lean rats, whereas relax ation in response to the calcium ionophore was similar in the corpulen t and lean animals. Aortic rings from corpulent and lean female rats s howed no differences in response to acetylcholine or to the calcium io nophore. Removal of endothelium resulted in the loss of relaxant respo nse to acetylcholine and the calcium ionophore. The relaxant responses to sodium nitrite were not significantly different in the corpulent a nd lean male rats when deendothelialized tissues were examined, but th e sensitivity to sodium nitrite was significantly lower in rings from corpulent male rats with intact endothelium. There were no differences in the response to bradykinin between corpulent and lean rats. These findings suggest that there is a specific impairment of endothelium-de pendent relaxation in the corpulent male rat that is limited to that m ediated by muscarinic receptors. The possibility that endothelium-deri ved contractile agents are secreted in the vessels of corpulent male r ats cannot be excluded.