| Background and objectives: Chronic administration with Nw-nitro-L-arginine methyl easter (L-NAIvIE) induces persistent hypertension, which is associated with a consequently deficient availability of nitric oxide, increased endothelin expression and oxidant stress. Statins, as an inhibitor of 3-hydroxyl-3-methylglutaryl coenzyme A reductase, have beneficial effects independent of lipid-lowering, including improving endothelial function, reducing oxide stress, et al. With a rat model, we designed this study to investigate the effects of statins on the remodeling of aorta in L-NAME -induced hypertension. Methods: Following groups(n=8) were divided: Control(C group), L-NAM.E (5Omg.kg?d?in water)(L group), L-NAME (SOmg.kg?d1 in water) plus Cerivastatin (0. lmg.kg1.d1 in water) (L+C group)or Simvastatin (5mg.kg?d?in water)(L+S group), Systolic blood pressure (SBP) was measured with tail-cuff method every other week. After 8 week, the levels of TG, IC, NOx, MDA in serum and El and AngII in plasma were measured. The contents of MDA and El in aortic tissue, the levels of iNOS and eNOS expression were determined. Results: (1) L group demonstrated a persistent, time-dependent elevation of SBP from base line (111.9 ?6.5mmHg) since second week(155.4?.lmmHgvs 109.3?.1 inmFlg; 162.0?5.4 mmflgvs 110.8?.9 mmHg; 166.0?.0 mrnHgvs 110.3 ?.3 rnrnHg; 183.0?.5 mmHgvs 112.9?.OmmHg; at 2,4,6, 8 week, P<0.01 respectively). Cerivastatin and simvastatin did not affect the blood pressure (150.3 ?10,2 mmHg, 151.0 ?9.3mmHg; 160.6 ?14.OmmHg, 146 ? 11.8mmHg; 172.3 ?8.3mmHg, 165.0 ?10.9mmHg; 183.9 ?12.4mmHg, 180.3 ?8. lmmHg at 2, 4, 6, 8 week, P>0.05 respectively ).(2) There was no significant difference in the levels of total triglyceride and cholesterol in serum among four groups. (3) After 8 week, L group showed a significantly increased ratio of media-to-cross-section area (0.307?.013 vs 0.215?0139 PKO.05) which were significantly improved by cerivastatin and simvastatin treatment (0.235 ?. 017, 0. 241 ?. 018, P<0. 05); the marked intimal thickness induced by L-NAME was -3- ameliorated by cerivastatin and simvastatin. (4) Although the levels of ET and AngII in plasma and NDA in serum were not altered by L-NAME(P>0.05), the concentrations of ET (134.36?16.66pg/ml vs 82.48?11.7Opg/ml, P<0.01) and MDA (34.69?.9lnmol/ml vs 6.16?1.66nmol /ml, P<0.01).were significantly increased in aorta in L group compared to C group. Cerivastatin and simvastatin significantly decreased the contents of ET (90.7?15.36pg/ml 8648?19.8lpgIml, P<0.01 respectively) and MDA (13.85 ?.75 nmol/ml 19 87?.56nmol/ml P<0.01 respectively), levels of eNOS (1.02?.095 vs 1.475? 117 P<0.01 respectively) and iNOS (0.352?.034 vs 1.094? 11 P<0.0l respectively) expression in arota, by Western blotting, were significantly increased in L group compared with C group; which were reduced by cerivastatin and simvastatin (eNOS, 1.137?.065, 1.164? 0.119, PKO.05 and P< 0.01, respectively; iNOS, 0.525?.044, 0.584?.046, P<0.01). However, level of NOx in serum from L group was lower than C group (8.31?.41 jimol/L vs 13,68? .28~tmol/L, P<0.0 1), cerivastatin and simvastatin treatment did not increase the level of NOx (9.02?.22p.molIL, 7.11?.69~tmol/L, P>0.05 respectively). Conclusion: Aortic remodeling in L-NAMIE-induced hypertensive rats were significantly ameliorated by a sub-lowering-lipid dose of statins, which may b... |
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