Scavenging Peroxinitrite Attenuates Angiotension II Induced Hypertension in rats

Angiotensin II (AngII) is known to induce both nitric oxide and superoxide productions and thus, the formation of peroxyinitrite (ONOO − ). To evaluate the contribution of ONOO − in the development of ANG II induced hypertension, we assessed arterial blood pressure (ABP) and renal excretory responses to chronic administration of AngII (65 ng/min) with or without co‐administration of a ONOO − scavenger, Mercaptoethyl guanidine (MEG; 3 μg/kg/min) for 2 weeks by osmotic minipump in Sprage Dawley rats. ABP was measured by tail‐cuff plethysmography and 24 hrs urine collections were made from metabolic cages at the start and on every 3 rd day of the experiment period. At the end of 2 weeks of experimental period, AngII infusion alone in rats significantly increased the mean ABP (119±2 to 179 ±3 mmHg; n= 6). This hypertensive response was significantly attenuated in rats co‐treated with MEG (115±2 to 154±6 mmHg; n=6). MEG or vehicle treatment alone did not alter ABP in these rats. Rats co‐treated with AngII+MEG showed a higher urinary excretion rate of sodium (3.1±0.2 vs 2.1±0.1 mmol/day at the 12 th day of treat) and lower excretion rate of 8‐isoprostane (28.8±5.5 vs 45.1±10.7 ng/day at the 12 th day of treatment) compared to rats treated with AngII alone. The rate of nitrate/nitrite was not significantly different between the groups. These results indicate a direct contributory role of ONOO‐ in mediating ANGII induced hypertension.