Contribution of Nitric Oxide to the Acute Antihypertensive Effect of Blockers of AT1 Angiotensin Receptors in Spontaneously Hypertensive Rats

The acute vasodepressor effect of AT1 angiotensin receptor blockers losartan and CL329167 was compared in spontaneously hypertensive rats (SHR) pretreated and not pretreated with NG-monomethyl-L-arginine (LNMMA; 15 mg/kg iv bolus plus infusion at 10 mg/kg/h), an inhibitor of nitric oxide (NO) synthesis. The antihypertensive effect of losartan (30 mg/kg, iv) in SHR pretreated with LNMMA (-13±4 mmHg) was greatly diminished (P<0.01) relative to the antihypertensive effect of losartan in SHR not pretreated with LNMMA (-44±8 mmHg). Similarly, the antihypertensive effect of CL329167 (5 mg/kg, iv) in SHR pretreated with LNMMA (-12±3 mmHg) was surpassed (P<0.01) by the antihypertensive effect in SHR not pretreated with LNMMA (-41±4 mmHg). However, pretreatment of SHR with LNMMA did not minimize the vasodepressor effect of prazosin, isoproterenol or sodium nitroprusside The impairment in