| Summary: | 碩士 === 國立陽明大學 === 生理學研究所 === 90 === The purpose of this study was to examine the roles of endothelin-1 (ET-1) and angiotensin II (AII), and their interaction in the enhanced vascular reactivity of aorta of insulin-infused rats. In the experiment, human insulin (1IU/12ml/day) was continuously infused into male Sprague-Dawley rats (250~300g) via subcutaneously implanted osmotic minipumps. The blood pressure（BP） and heart rate（HR）of rats were measured once a week by tail-cuff method. Then, oral glucose tolerance test（OGTT） was performed to monitor the development of insulin resistance in the rats. We found that the BP of rats was elevated two weeks after insulin infusion. After the hypertension of rats were induced, the animals were sacrificed and the vascular reactivity of aorta was studied by using vasoconstrictors ( including norepinephrine（NE）, KCl, ET-1, AII, and endothelin A（ETA）receptor antagonist BQ610, endothelin B（ETB）receptor antagonist BQ788, angiotensin type1（AT1）receptor antagonist losartan ) and vasodilators (including sodium nitroprusside（SNP）and acetylcholine（ACh）). The data showed that in rings of aorta with endothelium, the vasoconstriction induced by both ET-1 and AII were insignificantly increased. However, in rings of aorta without endothelium, the contractions induced by both ET-1 and AII were significantly increased. Then, by administrating the selective pretreatment BQ610 (10-6M) or losartan (10-6M) to a single concentration with AII or ET-1 in rings of aorta without endothelium, we found that pretreatment of BQ610 (10-6M) not only inhibited the vasoconstriction induced by ET-1, but also inhibited the vasoconstriction induced by AII, and that pretreatment of losartan (10-6M) could not inhibit the vasoconstriction induced by ET-1. Furthermore, the vasodilatation induced by SNP was about the same in the control group and the insulin-infused group, but the vasodilatation induced by ACh was significantly increased in the control groups. These results indicate that hyperinsulinemia and/or insulin resistance may produce endothelial dysfunction, and that the vasoconstriction induced by AII was likely mediated by ETA receptor.
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