VASCULAR RESPONSIVENESS IN YOUNG, DIABETIC, AND AGING HYPERINSULINEMIC RATS

The purpose of this study was to compare vascular responsiveness in yo ung (12 weeks old), aging hyperinsulinemic - glucose intolerant (52 we eks old) and diabetic (streptozotocin; 14 weeks old) rats. Aortic ring s with and without endothelium were maintained in organ chambers for i sometric tension recording. The contractile response to KCl was signif icantly enhanced in aortae from diabetic animals when compared to the responses obtained in young and old ones. The contractile response to norepinephrine or U46619, was significantly shifted to the right in th e aortae from aging animals, however the aortae from these hyperinsuli nemic rats were hyperresponsive to serotonin. Acetylcholine and ADP pr ovoked an endothelium-dependent relaxation to ADP was selectively inhi bited in the aging animals. The effect of sodium - nitroprusside was n ot significantly different in the three groups. Isoproterenol and fors kolin induced endothelium-independent relaxation. Isoproterenol respon ses were inhibited in aging and diabetic animals, however the forskoli n-relaxation was inhibited only in the aortae from aging animals. Thes e results suggest that in two models of diabetes (i.e. Type I insulin- dependent and type II non insulin-dependent) vascular responsiveness i s differently affected. Aging hyperinsulinemic animals present a selec tive hyperresponsiveness to serotonin, a selective dysfunction of ADP- induced endothelium-dependent relaxation and smooth muscle adenylate c yclase deficit. In diabetic animals a beta adrenergic hyporesponsivene ss, not linked to adenylate-cyclase dysfunction, and non-selective dep ression of endothelium-dependent responses can be observed.