|
(L - Arginine Restores Cyclosporine - Induced Impairment of Vascular Relaxation and cCMP Generation) |
Jong -un Lee , Kwang Ki Park , Ki Chul Choi , Kwangiay Yoo, Wonjae Kim , Kee - Young Lee , Hyun Kook , Soo Wan Kim , Nam Ho Kim , Yung Hong Baik |
|
Abstract |
The present study was airned at investigating interactions of cyclosporine (CsA) and L-arginine on the vascular relaxation and nitric oxide-cGMP responses. In the first series of experiments, rats were treated with CsA (25 mng kg ' day ', I.m.) for three weeks. They were supplied with drinking water either containing L-arginine (4 g/L) or none. Thoracic aorta was isolated and its isometric tension was examined. In another series of experiments, isolated thoracic aorta was treated with CsA in vitro (10 pg/mL, 60 min), and its isometric tension and tissue NO2/cGMP contents were deteimined. Aorticring preparations from the CsA-treated rats showed an attenuated acetylcholine- vasorelaxation, which was not afffeced by L-arginine-supplementation. Sodium nitroprus- side-relaxation was also attenuated. In the aortic preparations acutely treated with CsA in vitro (10 m g/mL, 60 min), the degree of acetylcholine-relaxation was significantly reduced, while sodium nitroprusside-relaxation remained unaltered. L-Arginine did not potentiate the acetylcholine-relaxation of the normal aortic ring, but completely restored the relaxation of the CsA-treated ring. L-Arginine alone also elicited a relaxation of the aortic ring in a dose-dependent manner, which was significantly attenuated by CsA-treatment. The vascular tissue NO2 contents were not significantly affected by CsA. The magnitude of increase in vascular tissue cGMP contents due to acetylcholine was significantly attenuated by CsA-treatment. L-Arginine restored, in part, the impaired cGMP response to acetylcholine. Sodium nitroprusside-induced formation of cGMP was also decreased in the presence of CsA, which was not significantly affected by L-arginine. It is suggested that CsA causes an L-arginine-sensitive impairment of vasorelaxation, the underlying mechanism of which is, in part, a decreased vascular capacity to generate cGMP in response to appropriate stimuli. |
|