Abstract 9359: Intrarenal Release of Superoxide Act Synergistically With Interstitial Angiotensin II to Promote Hypertension During Chronic Acidotic Conditions

Abstract

The capacity of chronic metabolic acidosis (CMA) to evoke hypertension has been previously evaluated. The superoxide mediated oxidative stress and the activation of intrarenal angiotensin II (Ang II), demonstrated a potential role in the pathogenesis of hypertension during CMA involving renal tubular sodium retention leading to volume expansion and strain to blood vessels. The primary focus of the present study was to determine whether the superoxide and the renal angiotensin II acts either synergistically or independently of each other to promote hypertension and the underlying mechanism of superoxide generation. Male Sprague Dawley Rats (100-150gms) were divided into four groups. Chronic acidosis was induced in all 4 groups by providing free access to ammonium chloride solution (0.28M) for 8 weeks in the drinking water. The second, third, and fourth groups were injected daily with captopril (12 mg/kg/day), tempol (100μmol/kg/day) and captopril+tempol respectively. After 8 weeks, blood and urine samples were collected for pH measurements and analyzed for sodium and potassium levels. Rats were anesthetized and in-line mean arterial pressure were determined. The renal cortical tissue homogenates from all four groups were analyzed for superoxide dismutase (SOD) and NADPH oxidase (NOX2) expression. Mean arterial pressure is significantly decreased in fourth group compared to the second and third groups. The serum sodium levels in fourth group were significantly reduced compared to the separately treated second and third groups, which suggested the declined reabsorption of sodium as the cause of decreased blood pressure in the fourth group. On the other hand, there was an increased SOD activity in the fourth group compared to the second and third groups, which implied intrarenal Ang II reduces the release of superoxide by increasing its dismutation. Moreover, our results demonstrated that there were no significant alterations in phagocytic NOX2 protein levels in all four treatment groups, which indicated that the superoxide release could be due to mitochondrial oxidative stress. Overall, blocking the release of intrarenal Ang II along with promoting the superoxide dismutation, showed a potential combined effect to control the observed hypertension.