Beneficial effect of pentaerythrityl tetranitrate on functional and morphological changes in the rat thoracic aorta evoked by long-term nitric oxide synthase inhibition.
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.
Török
Jozef
J
Institute of Normal and Pathological Physiology, Slovak Academy of Sciences, Sienkiewiczova 1, 813 71 Bratislava, Slovak Republic. torok@unpf.savba.sk
Kristek
Frantisek
F
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects; D006973:Hypertension / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D010417:Pentaerythritol Tetranitrate / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014665:Vasodilator Agents / Q000494:pharmacology*
D020030:Nitric Oxide Donors; D014665:Vasodilator Agents; D010417:Pentaerythritol Tetranitrate; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester