AGE-RELATED-CHANGES IN ENDOTHELIUM-DEPENDENT RELAXATION IN AORTA FROM GENETICALLY DIABETIC WBN KOB RATS

Experiments were designed to investigate the effects of aging and hyperglycemia on relaxation of the aorta for both endothelium-dependent and -independent agents in Wistar (control) and WBN/Kob (genetically diabetic) rats. The concentration of glucose in serum was elevated significantly in aged (90-92 wk) but not young (13-15 wk) WBN/Kob rats. Endothelium-dependent relaxations of both control and WBN/Kob rats to acetylcholine were reduced by aging. The relaxations induced by acetylcholine in aortic strips were significantly attenuated in both young (nondiabetic) and aged (diabetic) WBN/Kob rats, compared with those from age-matched control vessels, respectively. The concentration-response curves for sodium nitroprusside in aortic strips from both aged control and aged WBN/Kob rats were shifted to the left when compared with those from young rats, respectively. However, the maximal relaxation responses to sodium nitroprusside showed no difference among all vessels studied. The relaxations induced by sodium nitroprusside in aortic strips from both young and aged WBN/Kob rats were similar to those from age-matched control rats, respectively. The relaxations induced by atrial natriuretic peptide showed no difference among all vessels studied. In genetically diabetic rats, functional changes in endothelium occurred before elevation of the levels of glucose in the serum. Thus impaired endothelium-dependent relaxation may play an important role in the high incidence of vascular complications in diabetes mellitus.