ALTERATIONS OF NITRIC-OXIDE SYNTHASE EXPRESSION WITH AGING AND HYPERTENSION IN RATS

The activity and protein expression of endothelial nitric oxide syntha se (eNOS) and inducible NOS (iNOS) were investigated during the develo pment of hypertension in spontaneously hypertensive rats (SHR). SHR an d Wistar-Kyoto rats (WKY) were studied at three different ages: 4, 14 to 17, and 63 weeks of age. After treatment with saline or lipopolysac charide (LPS, 10 mg/kg IV) for 3 hours, the aortas were removed for me asurement of NOS activity and protein expression assay by [H-3]-L-citr ulline formation method and Western blot analysis, respectively. Plasm a levels of nitrite/nitrate (NO2-/NO3-) and tumor necrosis factor-alph a (TNF-alpha) were also determined. At 14 to 17 weeks and 63 weeks, th e basal activity and protein expression of eNOS in the aortas were sig nificantly lower in SHR than in WKY. In addition, the aged WKY exhibit ed lower eNOS activity than that of adult WKY, but this change was not seen in SHR. By comparison, the basal activity and protein expression of iNOS were only observed in SHR of the 14-to-17-week group and in t he 63-week group; SHR still exhibited higher activities, and these dif ferences were further exaggerated by treatment with LPS. The basal and LPS-induced NO2-/NO3- and TNF-alpha levels in the plasma were also hi gher in the SHR except the 4-week group. After treatment with quinapri l, the basal and LPS-induced expressions of iNOS in SHR were significa ntly attenuated. Our results demonstrated that alterations of activity and protein expression of eNOS and iNOS occurred in SHR. In addition, aging may reduce the activity of eNOS in WKY but not in SHR. The decl ine of eNOS activity and/or expression may contribute to the developme nt of hypertension, whereas the increase of iNOS expression may be a c onsequence of the pathological state of vessels associated with hypert ension in SHR. However, the augmented expression of iNOS in SHR was at tenuated by antihypertensive therapy, suggesting that the abnormal exp ression of iNOS is associated with hypertension.