Abstract
It is well established that hypertension is accompanied by cell death, however, less is known regarding the role of cell death in blood pressure (BP) control. Necrosis is an uncontrolled pathologic form of cell death that is associated with inflammation. Therefore, the goal of the current study was to test the hypothesis that necrosis contributes to the development of hypertension in SHR. Initial studies measured renal necrosis in 13 wk old male and female SHR (n=9) using flow cytometry. Male SHR had greater renal necrosis compared to female SHR (3.7±0.4% vs. 0.4±0.2% of total renal cells, respectively; p<0.0001). Additional male and female SHR were then randomized to receive vehicle or Necrox‐5 from 6–12 weeks of age (1 mg/kg via IP injection twice weekly; n=4); Necrox‐5 is a cell permeable inhibitor of necrosis that blocks oxidative stress induced necrotic cell death. BP was measured weekly via tail‐cuff analysis and via carotid catheter at sacrifice. Following 6 wks of treatment, kidneys were isolated and necrosis was measured by flow cytometry. Treatment with Necrox‐5 beginning at 6 wks of age attenuated maturation‐induced increases in BP in male SHR (Necrox‐5: 152±11 vs Control: 177±4 mmHg; p=0.07). BP in female SHR was not altered by chronic Necrox‐5 treatment (Necrox‐5: 152±14 vs. Control: 146±11 mmHg; p=0.72). In addition, the sex difference in BP apparent in control rats was abolished by Necrox‐5 treatment. Consistent with these results, Necrox‐5 treatment for 6 wks decreased renal necrosis only in males (Necrox‐5: 1.5±0.5% vs Control: 3±0% of total renal cells). Taken together, our data suggest that greater cell death in male SHR compared to female SHR contributes to sex differences in BP by exacerbating age‐related increases in BP in males.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
