Defective endothelium-dependent relaxation in the JCR:LA-corpulent rat.

Abstract

Endothelium-dependent relaxation of the aorta was assessed in JCR:LA-corpulent rats, which are hyperphagous, hyperlipidemic, hyperinsulinemic, and obese and spontaneously develop atherosclerotic disease and myocardial lesions. The findings in corpulent rats (6 months of age) were compared with those in age-and sex-matched lean rats. Aortic rings were prepared and mounted in Krebs-Henseleit buffer in a conventional organ bath. The tissue was contracted with norepinephrine (10(-6) mol/L), and relaxation was induced using acetylcholine, the calcium ionophore A23187, or bradykinin. The maximum relaxation to acetylcholine was impaired in corpulent male rats compared with lean rats, whereas relaxation in response to the calcium ionophore was similar in the corpulent and lean animals. Aortic rings from corpulent and lean female rats showed no differences in response to acetylcholine or to the calcium ionophore. Removal of endothelium resulted in the loss of relaxant response to acetylcholine and the calcium ionophore. The relaxant responses to sodium nitrite were not significantly different in the corpulent and lean male rats when deendothelialized tissues were examined, but the 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-dependent relaxation in the corpulent male rat that is limited to that mediated by muscarinic receptors. The possibility that endothelium-derived contractile agents are secreted in the vessels of corpulent male rats cannot be excluded.