| Summary: | 碩士 === 國立成功大學 === 藥理學研究所 === 88 === Blood pressure in diabetic rat is lower than normal rat. Muscarinic cholinoceptors (mAChRs) in the heart play an important role in the regulation of heart rate. Using the streptozotocin-(STZ-) treated rat, the model of IDDM, changes of mAChRs in the heart were elucidated to compare with normal rat.
The selective agonist of a1-adrenoceptor, phenylephrine, can stimulate cardiovascular reflex to decrease heart rate. The present study compared the baroreflex responses of heart to phenylephrine in the Wistar rats and STZ-induced diabetic rats. Baroreflex response to phenylephrine was higher in diabetic rats than that in Wistar rats. The selective agonist of M2 cholinoceptor, arecaidine propargyl ester hydrobromide (APE), was administrated to Wistar rat or STZ rat. APE-induced decrease of heart rate was more marked in diabetic rats. In addition, levels of mAChR protein and mRNA were enhanced in the heart of diabetic rats. The results suggested that M2-mAChR was highly expressed in diabetic rats.
Administration of insulin or phlorizin at concentration sufficient to lower the plasma glucose reversed the change of cardiac M2-mAChR in STZ-diabetic rats. Hyperglycemia was induced by administration of glucose into rats directly for 1 week (1g/kg,12 times per day, p.o.). The obtained results suggest that higher expression of M2-mAChR in diabetic rats might be related to hyperglycemia. Then, diabetic rats were intraperitoneally injected with aldose reductase inhibitor, ONO-2235 (100mg/kg/day) for 14 days. The levels of M2-mAChR protein and mRNA were also reversed. Moreover, the higher expression of M2-mAChR was obtained in rats receiving the administration of sorbitol (1g/kg, 12 times per day, i.p) for 1 week.
In conclusion, decrease of blood pressure in diabetic rat is related to the higher expression of cardiac M2-mAChR that may be stimulated by sorbitol and /or its metabolite from hyperglycemia.
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