Effects of rosuvastatin and amlodipine on blood pressure, serum levels of adma, hsp 90, caveolin-1 and vascular responsiveness including by phenylephrine, acetylcholine and angiotensin II in hypertension induced by nos inhibition and high salt diet

Oxidative stress and endothelial dysfunction play an important role in pathophysiology of hypertension. Statins which have cholesterol-lowering effects shown to increase the expression of eNOS and improve endothelial dysfunction by reducing the production of reactive oxygen. In our study is investigated to the effects of HMG-CoA reductase inhibitor rosuvastatin and the Ca channel blocker amlodipine on blood pressure, NADPH oxidase which is incresed by oxidative stress, rhokinase, asymmetric dimethylarginine (ADMA) as an endogenous inhibitor of NOS, caveolin-1 which inhibit to eNOS activity and heat shock protein 90 (hsp90) levels in the hypertensive rats. Furthermore in this study, phenylephrine contraction, acetylcholine relaxation and angiotensin 2 responses in isolated thoracic aortic vessels were evaluated. The effects of rosuvastatin compared with amlodipine. To form hypertension, L-NAME which is a nitric oxide inhibitor by intraperitoneally and drinking water containing 1% of salt was given to rats for 6 weeks. As from 2th week rats were applied intraperitoneally to 10 mg / kg / day rosuvastatin and to 10 mg / kg / day amlodipine for 4 weeks. Blood pressures were measured by the tail cuff method on 0, 14th, 28th and 42th days. NADPH oxidase, rhokinase, caveolin-1 and hsp90 levels of aortic tissue were measured by use of real-time PCR method and ADMA levels in serum were measured by ELISA. Blood pressures were observed as significantly higher in the 14th, 28th and 42th days in groups taking L-NAME and the salt, as significantly lower in amlodipine treatment groups in the 28th and 42th days, and as non-significantly lower in the rosuvastatin group in 42th day. Ach EC50 values were higher in hypertensive group. Ach Emax values have been observed lower in hypertensive group and significantly higher in the treatment groups. Levels of ADMA, NADPH oxidase, rhokinase and caveolin-1 significantly increased in hypertension group. Rosuvastatin and amlodipine significantly reduced these parameters but not ADMA. Level of hsp90 expression non-significant increased in hypertension group than the control group. DMSO application didn't constitute significant difference between groups. As a result rosuvastatin did not reduce blood pressure compared to amlodipine. But it has been observed that Ach Emax value was similar to amlodipine. Rhokinase, caveolin-1, hsp90, NADPH oxidase and ADMA levels might be mediated to blood pressure lowering effects of amlodipine. Rosuvastatin also similar to amlodipine may affect these parameters which associated with endothelial dysfunction and oxidative stress. Key words: Hypertension, Rosuvastatin, Amlodipine, Rhokinase, Caveolin-1, Hsp90, NADPH oxidase, ADMA