Impairment of endothelium‐dependent relaxation and changes in levels of cyclic GMP in aorta from streptozotocin‐induced diabetic rats

British Journal of Pharmacology - Tập 97 Số 2 - Trang 614-618 - 1989
Katsuo Kamata1, Noriyuki Miyata1, Yutaka Kasuya1
1Department of Pharmacology, School of Pharmacy, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142, Japan

Tóm tắt

Acetylcholine (ACh)‐induced relaxation of aortic strips with endothelium and production of cyclic GMP between streptozotocin‐induced diabetic and age‐matched control rats were compared. The concentration‐response curve for ACh‐induced relaxation was shifted to the right in diabetic rats. IC50 values for ACh were 4.57 ± 0.67 × 10−8 m and 1.00 ± 0.87 × 10−7 m in aortic strips from age‐matched control and diabetic rats, respectively (n = 6, P < 0.05). Relaxations produced by atrial natriuretic peptide (ANP) in diabetic aortae were similar to those in age‐matched vessels. Relaxations produced by sodium nitroprusside (SNP) in diabetic aortae were similar to those in age‐matched vessels. Basal levels of cyclic GMP and ACh‐induced production of cyclic GMP were significantly decreased in diabetic rats. These results suggest that functional changes in endothelium but not in guanylate cyclase activity in the aorta may occur in diabetes, and, thus, spontaneous and ACh‐induced formation of cyclic GMP may be decreased. This decrease in production of cyclic GMP may be responsible for the decreased response of the aorta to the relaxant effect of ACh.

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Tài liệu tham khảo

10.1139/y87-232

10.1161/01.RES.14.6.494

10.1097/00005344-198109000-00022

10.1016/S0002-9149(73)80051-7

10.1113/jphysiol.1981.sp013792

Dubowski K.M., 1962, An o‐toluidine method for body‐fluid glucose determination, Clin. Chem, 8, 215, 10.1093/clinchem/8.3.215

10.1111/j.1476-5381.1988.tb11548.x

10.1097/00005344-198406002-00008

10.1038/288373a0

10.1111/j.1476-5381.1987.tb10282.x

Ignarro L.J., 1984, Association between cyclic GMP accumulation and acetylcholine‐elicited relaxation of bovine intrapulmonary artery, J. Pharmacol. Exp. Ther, 228, 682

10.1139/y85-199

10.1248/bpb1978.11.707

10.1007/BF00172117

10.1161/01.HYP.5.6.881

10.1016/S0021-9258(19)52451-6

10.1016/0014-2999(86)90013-0

Pfaffman M.A., 1982, Insulin reversal of diabetes‐induced inhibition of vascular contractility in the rat, Am. J. Physiol, 242, S490

10.1161/01.RES.52.3.352

Scarborough N.L., 1984, Nifedipine and alpha2‐adrenoceptors in rat aorta. II Role of extracellular calcium in enhanced alpha2‐adrenoceptor‐mediated contraction in diabetes, J. Pharmacol. Exp. Ther, 236, 603

10.1016/0002-9343(79)90734-4

10.1159/000138197

10.1097/00004872-198410000-00015

10.1073/pnas.81.23.7661

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Thông tin xuất bản

British Journal of Pharmacology

Tập 97 Số 2

614-618

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