The effect of perindopril, losartan, novokinin on blood pressure,eNOS, ADMA, Rhokinaz, NADPH oxidase and the vascular responses including ATII receptor in hypertension induced by NOS inhibition and salt

ABSTRACTTHE EFFECT OF PERINDOPRIL, LOSARTAN, NOVOKININ ON BLOOD PRESSURE,eNOS, ADMA, RHOKINASE, NADPH OXIDASE AND THE VASCULAR RESPONSES INCLUDING ATII RECEPTOR IN HYPERTENSION INDUCED BY NOS INHIBITION AND SALTIn our study, we investigated the roles of NADPH oxidase, Rho kinase activities, eNOS (endothelial nitric oxide synthase), asymmetric dimethylarginine (ADMA) level and the effects of ACE inhibitor (perindopril), AT1 receptor blockade (losartan), AT2 receptor agonist (novokinin) on these enzymes and blood pressure in hypertension induced by NOS inhibition and salt. Furthermore, in the isolated thoracic aorta rings of all groups, phenylephrine induced contractile, acetylcholine induced dilator responses and the role of AT2 receptor and Rho kinase on angiotensin II induced contraction was investigated.To develop hypertension, L-NAME was administrated intraperitoneally, salt was given with drinking water (1%) for 4 weeks. Perindopril (2mg/kg/day), losartan (2mg/kg/day), novokinin (0,1mg/kg/day), were administrated intraperitoneally for 2 weeks. Blood pressure was measured by using tail-cuff method; NADPH oxidase, Rho kinase, protein arginine methyltransferas (PRMT) ADMA synthesizing enyzme, eNOS levels were measured by Real-Time Polymerase Chain Reaction in aortic tissues.Blood pressure increased significantly in L-NAME and salt administrated groups at 14th and 28th days. In treated hypertensive groups, blood pressure reduced at 28th day significantly. The levels of Rho kinase and PRMT expression increased and the level of eNOS expression decreased in hypertensive group, but It was not significantly. L-NAME and salt administration increased EC50 value of acetylcholine dilatation, decreased Emax value significantly. In treated hypertensive groups, EC50 decreased, Emax increased significantly.The effect of AT2 receptor agonist novokinin on blood pressure was similar to losartan. Acetylcholine sensitivity was higher in novokinin than losartan treatment group. The measured levels of these parametres were similar in novokinin and perindopril groups. These results suggest that novokinin may test in cardiovascular disease in terms of protective effects.Key Words: Hypertension, nitric oxide, novokinin, rhokinase, ADMA