Mechanism underlying enhanced endothelium-dependent vasodilatation in thoracic aorta of early stage streptozotocin-induced diabetic mice

AIM: To investigate the mechanism of the enhanced endothelium-dependent vasodilatation in thoracic aorta of the early stage streptozotocin (STZ)-induced diabetic C57BL/6J mice. METHODS: Radioimmunity was used to detect the metabolite of prostaglandin I2 (PGI2), 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), in the blood serum. Vascular muscle tension and phenylephrine (PE)-induced rhythmic activity in the isolated thoracic aorta of mice were also compared. RESULTS: 6-Keto-PGF1 alpha in the serum was significantly higher in STZ-induced diabetic mice than age-matched controls (1.8+/-1.0) microg./L vs (0.5+/-0.3) microg/L, P<0.01]. PE induced rhythmic activity in both diabetic and control mouse aorta but the amplitude was markedly higher in diabetic mice than in controls (4.9+/-1.7) % vs (12+/-5) %, P<0.01]. PE, high K+ solution-induced contraction, and acetylcholine (ACh)-induced relaxation (56+/-10) % vs (81+/-8) %, P<0.01] were notably enhanced in diabetic mice than those in controls. Alone NG-nitro-L-arginine methyl ester (L-NAME) or 6-(phenylamino)-5,8-quinolinedione (LY-83583) abolished the rhythmic activity and ACh-induced relaxation in controls but only partially inhibited them in diabetic mice. Indomethacin did not affect rhythmic activity but depressed ACh-induced relaxation. L-NAME plus indomethacin significantly depressed the rhythmic activity and ACh-induced relaxation than L-NAME alone (P<0.01). Furthermore tetraethylammonium plus L-NAME abolished them in diabetic mice. CONCLUSION: The mechanism that enhanced endothelium-dependent vasodilatation in STZ-induced diabetic mice is due to enhanced production of PGI2 and endothelium-derived hyperpolarizing factor (EDHF). The phenomena maybe only take place in early stage of diabetic mice.