Valsartan is a specific angiotensin n (ATII) antagonist acting at SUbtype I of AT receptors. It has a dose dependent potent and long lasting blood pressure lowering effect and is used as an effective once daily medication for the treatment of hypertension. It has been suggested that mechanisms other than blockade of the ~ascular ~T1 re~eptors s,:btype may aJ~o contrIbute to Its antIhypertensIve effect. ThIS study was designed to demonstrate the doseeffect relationshio of valsarran on MAP (mean arterial pressure)" of freely moving chronically instrumented conscious rats. The involvement of the sympathetic nervous system, the endothelium derived releasing factor (EDRF) known as nitric oxide (NO) and prostaglandins in such effect was also investigated. The dependence of valsartan action on calcium or potassium entry through their specific channels was also explomd. Infusion of vaIsartan (loo ug/kg/min) for 10 min aboiished the pressor effect of ATII in 4 doses of 1,3,10 and 30 ng/kg and substantially shifted noradrenaline dose-response curves (10,30,100 and 300 ng/kg) to the right. Valsartan bolus injectL,n in 4 successive doses (10,30,100 and 300 ug/kg) produced dose dependent reduction of MAP elevated and maintained by AT, NA infusion or the nitric oxide synthase inhibitor, NG-nitro-L-arginine methyl ester |
