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Experiments were designed to characterize endothelium-dependent relaxation in thoracic aortic rings obtained from streptozotocin-induced diabetic rats. When the degree of the peak relaxation was compared, the endothelium-dependent relaxant responses to acetylcholine, histamine, or ADP in precontracted aortic rings showed that there was no significant difference between diabetic and control vessels. However, the time courses appeared quite different. The endothelium-dependent relaxant responses in diabetic vessels were more transient than those in control vessels. In addition, the rapid fade of the endothelium-dependent responses observed in diabetic vessels was significantly suppressed by pretreatment with superoxide dismutase. Pretreatment with catalase, deferoxamine, allopurinol, or indomethacin did not prevent the rapid fade of the endothelium-dependent relaxation. The endothelium-independent relaxation induced by nitric oxide also faded more quickly in diabetic vessels; this impairment was less pronounced in the presence of superoxide dismutase. These results suggest that the transient nature of the endothelium-dependent relaxation is more marked in diabetic rat aorta as a result of an enhanced accumulation of superoxide anion.

The aim of this study was to determine how the contractile responses to 5-hydroxytryptamine (5-HT) are altered in aortas from rats with streptozotocin-induced diabetes and to explore the possible mechanisms of the altered vascular reactivity to 5-HT in diabetes. In the presence of extracellular Ca²⁺ (2.5 mM), the contractile responses to stimulation of 5-HT₂ receptors with 5-HT were greater in aortas from diabetic rats as compared with those from age-matched controls. Similarly, phorbol-12, 13-dibutyrate (PDBu) (≧30 nM) induced significantly greater contractions in diabetic aortas. The enhanced contractile responses of diabetic aortas to 5-HT and PDBu were abolished in the presence of 1 µM nifedipine. Pretreatment with 20 nM staurosporine caused a complete inhibition of the contractile responses to 5-HT in both control and diabetic aortas. In contrast to those to 5-HT and PDBu, the contractile responses to high K⁺ (40 mM) were markedly diminished in diabetic aortas. The nifedipine-sensitive uptake of ⁴⁵Ca²⁺ induced by 5-HT was significantly greater in diabetic aortas than in controls, whereas that induced by high K⁺ was significantly less in diabetics. The phasic contractions produced by 5-HT in Ca²⁺-free medium were significantly attenuated in diabetic aortas, but those produced by norepinephrine were unchanged. Accumulation of [³H]inositol monophosphate (IP₁) in aortic strips prelabeled with myo-[³H] inositol was increased to a similar extent by 5-HT and norepinephrine in control rats, but the 5-HT-induced increase in [³H]IP₁ accumulation was significantly less than the norepinephrine-induced one in diabetics. These findings indicate that the extracellular Ca²⁺-dependent contractions mediated by 5-HT₂ receptors are enhanced in aortas from diabetic rats, and this is presumably related to a greater influx of Ca²⁺ through transmembrane Ca²⁺ channels as a consequence of increased protein kinase C activated processes. On the other hand, the contraction induced by release of Ca²⁺ from intracellular stores in response to 5-HT is diminished in these tissues, possibly due to the impaired phosphoinositide response.

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