| First Author | Gatineau E | Year | 2019 |
| Journal | Am J Physiol Heart Circ Physiol | Volume | 316 |
| Issue | 3 | Pages | H506-H515 |
| PubMed ID | 30550352 | Mgi Jnum | J:271777 |
| Mgi Id | MGI:6280078 | Doi | 10.1152/ajpheart.00473.2018 |
| Citation | Gatineau E, et al. (2019) Losartan prevents the elevation of blood pressure in adipose-PRR deficient female mice while elevated circulating sPRR activates the renin-angiotensin system. Am J Physiol Heart Circ Physiol 316(3):H506-H515 |
| abstractText | Deletion of the prorenin receptor (PRR) in adipose tissue elevates systolic blood pressure (SBP) and the circulating soluble form of PRR (sPRR) in male mice fed a high-fat (HF) diet. However, sex differences in the contribution of adipose-PRR and sPRR to the regulation of the renin-angiotensin system (RAS) in key organs for blood pressure control are undefined. Therefore, we assessed blood pressure and the systemic and intrarenal RAS status in adipose-PRR knockout (KO) female mice. Blockade of RAS with losartan blunted SBP elevation in HF diet-fed adipose-PRR KO mice. ANG II levels were significantly increased in the renal cortex of HF diet-fed adipose-PRR KO female mice, but not systemically. HF diet-fed adipose-PRR KO mice exhibited higher vasopressin levels, water retention, and lower urine output than wild-type (WT) mice. The results also showed that deletion of adipose-PRR increased circulating sPRR and total hepatic sPRR contents, suggesting the liver as a major source of elevated plasma sPRR in adipose-PRR KO mice. To mimic the elevation of circulating sPRR and define the direct contribution of systemic sPRR to the regulation of the RAS and vasopressin, C57BL/6 female mice fed a standard diet were infused with recombinant sPRR. sPRR infusion increased plasma renin levels, renal and hepatic angiotensinogen expression, and vasopressin. Together, these results demonstrate that the deletion of adipose-PRR induced an elevation of SBP likely mediated by an intrarenal ANG II-dependent mechanism and that sPRR participates in RAS regulation and body fluid homeostasis via its capacity to activate the RAS and increase vasopressin levels. NEW & NOTEWORTHY The elevation of systolic blood pressure appears to be primarily mediated by cortical ANG II in high-fat diet-fed adipose-prorenin receptor knockout female mice. In addition, our data support a role for soluble prorenin receptor in renin-angiotensin system activation and vasopressin regulation. |
