Acetazolamide Administration Restores the Blood Pressure Lowering Effect of Tempol in Female SHR

Abstract

The mechanisms responsible for the sex differences in blood pressure (BP) in humans are not clear. Over the past several years, we have studied the spontaneously hypertensive rat (SHR) as a model of sex differences in BP control. Oxidative stress (OS) plays a major role in BP regulation in preclinical studies. There is a sex difference in the BP responses to pro‐oxidants and antioxidants in the SHR. In contrast to males, BP in female SHR does not decrease in response to Tempol or Apocynin. Acetazolamide (Aceta) inhibits proximal tubular sodium reabsorption, increasing sodium delivery to the distal tubule which increases distal tubule OS. We tested the hypothesis that an increase in sodium delivery in the distal tubule will restore the BP lowering effects of Tempol in female SHR.Materials and MethodsFemale SHR, aged twenty weeks, were implanted with radiotelemetry transmitters and following a two week recovery period, baseline mean arterial pressure (MAP) was measured 24 hrs per day. All rats were then given Aceta (100 mg/kg/day sc) for 14 days (n=14). After this period, a group of rats were randomized to receive Tempol (1mmol/L) in drinking water for an additional two weeks (Aceta + Tempol) (n=7/grp) and BP was compared to controls who received Aceta only (n=7/grp). MAP was measured continuously throughout the treatment periods.ResultsAt baseline, MAP was similar in both groups of female SHR (144 ± 1 vs. 145 ± 1 mmHg). Aceta administration for two weeks caused a 10 mmHg reduction in MAP, which was similar in both group of rats (132 ± 1 vs. 131 ± 1 mmHg, p=0.43). Tempol administration significantly lowered MAP in presence of Aceta (138 ± 1vs. 122 ± 1 mmHg, p<0.0001). Body weight was similar between Aceta and Aceta + Tempol groups (200.3 ± 2.0g vs. 192.2 ± 4.0 g).In conclusion, our data suggest that there are sex differences in proximal sodium reabsorption that may impact OS in SHR. By increasing sodium delivery to the distal nephron with acetazolamide, the BP lowering effect of Tempol is restored in female SHR. These data suggest that different mechanisms may control oxidative stress and blood pressure in male and female SHR.Support or Funding InformationThis project was funded by NIH R01 HL135089, P20 GM12334, & PO1HL51971This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.