Blood Pressure in Old Female SHR is not Salt Sensitive and Tempol Fails to Decrease Blood Pressure during High Salt Intake

Abstract

Oxidative stress contributes to the development and maintenance of hypertension in male rodents; however studies in females have rarely shown a reduction in blood pressure (BP) with antioxidants. Tempol, a superoxide dismutase mimetic, decreases BP in young male spontaneously hypertensive rats (SHR), but fails to reduce BP in either young or old female SHR, despite the fact that females have similar or higher levels of oxidative stress markers. In contrast, recent experiments from our laboratory have shown that Tempol decreases BP in old female SHR treated chronically with Acetazolamide. Acetazolamide is a carbonic anhydrase inhibitor that increases sodium delivery to the distal nephron and may increase distal oxidative stress. Thus the data suggest that oxidative stress‐mediated BP control is dependent on increased sodium delivery to the distal nephron. The aim of the present work was to test the hypothesis that tempol will decrease blood pressure in old female SHR chronically given a high salt intake. Female SHR (20 months of age) were divided into two groups (n=7/group): Control + Tempol (C+T), and High Salt Diet + Tempol (HSD+T). After baseline mean arterial pressure (MAP; telemetry; 5 days), rats received low salt diet (NaCl 0.3%; C+T) or high salt diet (NaCl 8%; HSD+T). On day 22, rats in both groups (C+T and HSD+T) were given tempol (30 mg/kg/d) in the drinking water for 21 days. Baseline MAP was similar between groups (C+T: 174±7; HSD+T: 168±5 mm Hg, p=NS), and MAP was not salt sensitive (C+T: 178±5; HSD+T: 178±4 mm Hg, p=NS). Tempol treatment had no effect on MAP in either group of female SHR (C+T: 179±5; HSD+T: 178±5 mm Hg). Because tempol in acetazolamide treated female SHR reduces MAP, whereas tempol has no effect on MAP in females on high salt diet, the data suggest that in hypertensive female rats, tempol reduces MAP only when proximal sodium reabsorption is blocked.Support or Funding InformationSupported by NIH‐R01HL66072, PO1HL51971 (JFR), 14POST18640015 (ROM).