1P286 Long term effects of hypotensive drugs, captopril and hydralazine, on endothelial function in SHRSP

After a 8-week treatment with captopril (80 mg/kg/day) or hydralazine (80 mg/kg/day) in SHRSP and WKY, ACh- or nitroglyceline-induced vasodilations in the isolated thoracic aortae were measured with special reference to NO. The expressions of eNOS, iNOS, and nNOS proteins and nitrotyrosine, a marker of peroxynitrite, were detected by immunostaining method. Both of the SBPS of captopril- or hydralazine-treated SHRSP were decreased to a similar degree. Serum NOx concentration in untreated SHRSP was higher than that of WKY. The rised NOx in serum was attenuated by captopril treatment, but not hydralazine treatment. ACh-induced endothelium-dependent relaxation in the thoracic aortae of SHRSP was attenuated in comparison with that of WKY. The attenuation of ACh-induced vasodilation was repaired by the administration of captopril, but not hydralazine. There were no differences in nitroglycerine-induced endothelium-independent relaxation between SHRSP and WKY. Superoxide anion production in the thoracic aortae from SHRSP was enhanced in comparison with that in WKY. These changes were diminished by captopril and hydralazine treatments . Nitrotyrosine and iNOS proteins in the thoracic aortae of SHRSP were decreased by captopril, but not hydralazine, although the expression of eNOS was no difference between the groups. Thus, captopril treatment restored endothelial disorder through not only hypotensive effect but also modulation of NOSs expressions.