Altered Resting Nitric Oxide Vasodilator Tone in Two-Kidney, One Clip Rats / 대한신장학회잡지

ABSTRACT

Endogenous nitric oxide(NO) plays an important role in the regulation of blood pressure. It has been known that the evoked NO-dependent dilator system may be impaired in various hypertensive models. The effects of NG-nitro-L-arginine(L-NNA), lipopolysaccharide(LPS) and tempol on mean arterial pressure(MAP) and the effects of L-NNA on isolated aorta tone were studied in order to elucidate potential alterations in resting vasodilator tone of NO in two-kidney, one clip(2K1C) hypertension. Plasma nitrite/nitrate levels were measured by colorimetric assay, and the expression of endothelial and inducible NO synthases(eNOS, iNOS) was determined by Western blot analysis. L-NNA caused an increase of MAP, while LPS produced a hypotensive effect in both 2K1C and control rats. The magnitude of the pressor or depressor response to L-NNA and LPS was comparable in the two groups. Tempol induced a sustained decrease in MAP in 2K1C rats, while it had no effects on MAP in control rats. Plasma concentrations of NO metabolites were significantly increased following the LPS-treatment in both 2K1C and control rats, while they were not affected by tempol-treatment. In endothelium-intact aortic rings precontracted with 25 mM KCl, L-NNA caused a dose-dependent contraction. The magnitude of the maximal contraction was attenuated in 2K1C rats as compared with control. An inhibition of contractile responses to L-NNA in the hypertensive group was also shown in rubbed rings, although the magnitude of contractions was markedly reduced. The vascular expression of both eNOS and iNOS was significantly decreased in 2K1C rats as compared with control. These results indicate that 2K1C hypertension is associated with a reduced basal vasodilator tone of NO and a decrease in the vascular expression of NOS isozymes.