Abstract P081: Tempol Decreases Blood Pressure in Aged Female SHR When Treated With Acetazolamide
Oxidative stress contributes to the development and maintenance of hypertension in male rodents, but studies in females have rarely shown a reduction in blood pressure (BP) with antioxidants. Tempol, a superoxide dismutase mimetic, decreases BP in young male 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. The reason for the sex difference in the response to tempol remains unclear. Acetazolamide inhibits carbonic anhydrase in the proximal tubule thus increasing sodium delivery to the distal nephron, and thereby should increase distal oxidative stress. Acetazolamide was used to test the hypothesis that with increased sodium delivery to the distal nephron, tempol would reduce the BP in aging female SHR. Female SHR, 20-22 mos old, were divided into three groups (n=4-6/grp): Control (C), Acetazolamide (A), and Acetazolamide+Tempol (A+T). After baseline mean arterial pressure (MAP; telemetry), rats received vehicle (C) or acetazolamide (A and A+T). On day 8, rats in C and A+T groups were given tempol (30 mg/kg) for 11 days. Baseline MAP was similar (C: 170±7; A: 182±4; A+T: 172±6 mm Hg, p=NS). Tempol had no effect on MAP in C+T, but reduced MAP in A+T group (C+T: 169±1; A: 171±1; A+T: 151±5 mm Hg; p<0.005 A+T vs A, C+T). Basal renal oxidative stress measured by lucigenin chemiluminescence was not different in the groups; NADPH-stimulated oxidative stress was decreased in A+T compared to A and C+T (C+T: 641.8±72.2; A: 499.3±18.3; A+T: 406.2±56.3 RLU/mg/min; p<0.05, A+T vs A, C+T). Plasma total antioxidant capacity was increased by tempol only in A+T rats (C+T: 59.07±9.67; A: 69.01±4.66; A+T: 118.24±18.38 nmol/μl; p<0.05, A+T vs A, C+T). Thus tempol is capable of modestly reducing MAP in aging female SHR when proximal sodium reabsorption is blocked. The data suggest that oxidative stress-mediated BP control is dependent on increased sodium delivery to the distal nephron. Because hypertension in male SHR is attenuated with tempol alone, but not in females, taken together, the data suggest sex differences in sodium handling and thus localization of oxidative stress production in the kidneys of SHR. Supported by NIH-R01HL66072, PO1HL51971 (JFR), 14POST18640015 (ROM).
Author Disclosures: C. Dalmasso: None. R.O. Maranon: None. C.N. Patil: None. A. Harris: None. H. Zhang: None. C.S. Wilcox: None. J.F. Reckelhoff: None.
This research has received full or partial funding support from the American Heart Association, Greater Southeast Affiliate (Alabama, Florida, Georgia, Louisiana, Mississippi, Puerto Rico & Tennessee).
- © 2015 by American Heart Association, Inc.