Effects of melatonin on blood pressure, serum level of ADMA, NADPH oxidase, Rho kinase, Hsp90, caveolin-1 levels and vascular response in NOS inhibition and salt induced hypertension

In this study, it has been aimed to investigate the effects of melatonin on the activities of rho kinase, NADPH oxidase, Caveolin-1(Cav-1), hsp90 and on the levels of ADMA and on the blood pressure in N-nitro-L-arginine metil ester (L-NAME) and salt induced hypertensive rats. In addition to this, in vitro phenylephrine (phe) contraction and acetylcholine (Ach) relaxation responses in the aorta of rats subjected to the pharmacological treatment and developed hypertension were investigated. In hypertension model, %1 salt in drinking water was given by oral route and L-NAME (40 mg/kg/gün) were injected intraperitoneally (i.p.) for six weeks. Melatonin was applied for 4 weeks (10mg/kg/day) intraperitoneally (after 14th day in hypertension group). Blood pressure was measured by tail-cuff method. Levels of NADPH oxidase, rho kinase, Cav-1 ve hsp90 were measured in aort tissue by RT-PCR. ADMA was measured from the serum by ELISA. Blood pressure of the rats in hypertension group exhibites a significantly increase compared with control group on 14th (141,63±8.3; 97,33±0,84), 28th (147,71±2; 96,50±0,9295) and 42th (151,9±7,5; 100±1,41) days. On the other hand, blood pressure of melatonin group exhibites significantly decrease on 28th (124,11±5,9; 147,71±1,97) and 42th (116,43±3,9; 151,90±7,53) days compared with hypertension. It was observed that Ach Emax value of melatonin group is higher than the values of the control group and the hypertension group. However, a significantly statistical difference for Ach EC50 between three group was not observed. The observation that the levels of ADMA, rho kinase, NADPH oxidase, hsp90 and Cav-1 expression are higher in the hypertensive group can be explained by the existance of some molecules that causes the blood pressure to increase. Since it was observed that the melatonin decreases the blood pressure caused by NOS inhibition and salt injection, increases the vascular Ach sensitivity compared to hypertension and control group, and effects the levels of ADMA, rho kinaz, NADPH oksidaz, hsp90 and Cav-1 expression positively, it can be claimed that melatonin can be used in hypertension treatment as a new treatment approach. Key words: Hypertension, nitric oxide, melatonin, NADPH oxidase, Rho kinase, ADMA, Hsp90, caveolin-1