Abstract
Dietary nitrite and nitrate have been recently implicated as an important source of nitric oxide with antihypertensive effects. We have previously shown acute antihypertensive effects exerted by a single oral dose of sodium nitrite (NaNO 2 ) in renovascular hypertension. However, the possible chronic antihypertensive effects of NaNO 2 have not been examined yet. We evaluated the effects of NaNO 2 on L-NAME (Nω-Nitro-L-arginine methyl ester)-induced hypertension in Wistar rats. METHODS: Rats received vehicle (tap water) or L-NAME (1g/L) in their drinking water. After two weeks of treatment, the rats received NaNO 2 (15 mg/kg/day by gavage) or vehicle for 4 weeks. Systolic blood pressure (SBP) was evaluated by pletismography weekly. Plasma levels of nitrate and nitrite were assessed by Griess reaction and ozone-based chemiluminescence, respectively. Dihydroethidium (DHE) was used in aortic sections to evaluate reactive oxygen species (ROS) production by fluorescence microscopy. Results: while NaNO 2 treatment induced no changes on SBP in vehicle-treated rats (p>0.05), this treatment significantly reduced SBP in L-NAME-treated rats (192±2 mmHg in L-NAME + vehicle group versus 164±2 mmHg in L-NAME + nitrite group; P<0.05). At the end of treatment, we found lower plasma nitrite levels in L-NAME rats compared with normotensive controls (148±14 nM versus 445±97; P<0.05). NaNO 2 treatment increased plasma nitrite levels in both normotensive controls and in L-NAME-treated rats (P<0.05). While no significant changes were found in plasma nitrate levels in L-NAME-treated rats when compared with controls (903±157 nM versus 995±145; p>0.05), NaNO 2 treatment induced significant increases in plasma nitrate levels in both normotensive and hypertensive rats (191±13 nM and 199±17 respectively; p<0.05 when compared to the controls). When compared to the control groups, higher ROS levels were found in the aortic rings from L-NAME treated rats (4091±249 A.U. versus 5709±598 A.U.; p<0.05) but treatment did not affect this increase (p>0.05). Conclusion: Our results show for the first time that NaNO 2 has relevant chronic antihypertensive effects in L-NAME hypertension. However, was unable to reverse the oxidative stress associated with L-NAME-induced hypertension.
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