High plasma soluble prorenin receptor (sPRR) levels correlate with systolic blood pressure in aged male but not in female mice

Abstract

Elderly subjects are predisposed to intrarenal renin‐angiotensin system (RAS) activation, which increases the risk for hypertension, kidney injury, and chronic kidney disease (CKD). The prorenin receptor (PRR), a component of the RAS that enhances the activity of renin and fully activates prorenin, is upregulated in the kidney in hypertensive rodent models. PRR possesses two molecular forms, a cell membrane bound and a soluble form (sPRR). Levels of sPRR in plasma are elevated in patients with cardiovascular diseases, including hypertension, preeclampsia, diabetes, and CKD. In the present study we tested the hypothesis that age increases plasma sPRR, blood pressure, and renal function in mice. We used male and female C57Bl/J6 mice distributed in 4 groups according with age (months, m) and sex (♂/♀) as follows: 1) 4–6 m, N=8/5; 2) 8–10 m, N=8/7; 3) 15–19 m, N=12/7; and 4) +20 m, N=9/7. Systolic blood pressures (SBP, mm Hg) measured by the tail cuff method were increased in male mice in 15–19 m (118±1.9) and +20 m (129±2.9) groups, compared to 4–6 m (103.0±1.8) and 8–10 m (105.0±1.6); p<.0001). No significant changes in SBP were observed in females. SBP positively correlated with age in male mice only (r=0.669; p=0.001). Plasma sPRR levels measured by ELISA (IBL America, Inc) did not differ between male and female young mice (10 m or younger). However, plasma sPRR levels were significantly higher in male mice of 15–19 m (3.8±0.2 ng/ml) and even greater in older mice (+20 m: 4.9±0.4 ng/ml), compared to 4–6 m (1.8±0.2 ng/ml) and 8–10 m (1.8±0.1 ng/ml) (p<.001). In contrast, only female mice older than 20 m of age showed significant increased plasma sPRR (4.3±0.1 ng/ml) compared to younger mice (p=0.03). Interestingly, plasma sPRR was positively correlated with SBP (r=0.602, p=0.02) in males but not in females. No differences were found in plasma and urine creatinine, osmolality, and BUN, or in urinary sodium concentration and proteinuria among groups. We conclude that: 1) Age positively correlates with SBP in male mice but not in females; 2) Plasma sPRR levels increase with age in male and female mice; and 3) Plasma sPRR levels are associated with SBP in aged males but not in female mice. The data suggests that age‐associated increases in plasma levels of sPRR and SBP are more sensitive to advanced age in male than in female C57Bl/6J mice. Further studies are needed to define whether hormone effects on plasma sPRR and SBP are independent or not of age.Support or Funding InformationSupport from NIH‐NIDDK (R01DK104375) to MCP; NIH‐NIA (R01AG047296) to RMThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.