Beneficial effect of pentaerythrityl tetranitrate on functional and morphological changes in the rat thoracic aorta evoked by long-term nitric oxide synthase inhibition.

摘要

The present study examined whether pentaerythrityl tetranitrate (PETN), a tolerance-devoid exogenous donor of nitric oxide (NO), could attenuate functional and morphological changes in the rat thoracic aorta evoked by 6-week NO synthase inhibition by NG-nitro-L-arginine methyl ester (L-NAME). Systolic blood pressure in L-NAME + PETN-treated rats (163 +/- 1 mm Hg) was significantly lower than in L-NAME-treated rats (172 +/- 2 mm Hg) but was still higher than in age-matched controls (126 +/- 2 mm Hg). Six weeks of treatment of rats with L-NAME significantly inhibited endothelium-dependent relaxation of the isolated thoracic aorta induced by acetylcholine. The inhibitory effect of L-NAME was entirely reversed by the simultaneous treatment with PETN. The enhancing effect of L-NAME on noradrenaline-induced contraction was antagonised by long-term treatment with PETN. Wall thickness, cross-sectional area and wall/diameter ratio of the thoracic aorta in L-NAME-treated rats were markedly increased. In the L-NAME + PETN-treated rats, the increment of these parameters was significantly lower. The results suggest that PETN administered to rats during development of NO-deficient hypertension prevented functional impairment and at the same time reduced structural changes in the thoracic aorta induced by long-term inhibition of NO synthase.