Vascular responsiveness in young, diabetic, and aging hyperinsulinemic rats

The purpose of this study was to compare vascular responsiveness in young (12 week old), aging hyperinsulinemic-glucose intolerant (52 weeks old) and diabetic (streptozotocin; 14 weeks old) rats. Aortic rings with and without endothelium were maintained in organ chambers for isometric tension recording. The contractile response to KCl was significantly 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 the aortae from aging animals, however the aortae from these hyperinsulinemic rats were hyperresponsive to serotonin. Acetylcholine and ADP provoked an endothelium-dependent relaxation which was markedly depressed in the aortae from diabetic animals. The relaxation to ADP was selectively inhibited in the aging animals. The effect of sodium-nitroprusside was not significantly different in the three groups. Isoproterenol and forskolin induced endothelium-independent relaxation. Isoproterenol responses were inhibited in aging and diabetic animals, however the forskolin-relaxation was inhibited only in the aortae from aging animals. These results suggest that in two models of diabetes (i.e. Type I insulin-dependent and type II non insulin-dependent) vascular responsiveness is differently affected. Aging hyperinsulinemic animals present a selective hyperresponsiveness to serotonin, a selective dysfunction of ADP-induced endothelium-dependent relaxation and smooth muscle adenylate cyclase deficit. In diabetic animals a beta adrenergic hyporesponsiveness, not linked to adenylate-cyclase dysfunction, and non-selective depression of endothelium-dependent responses can be observed.