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. 2019 Mar 1;316(3):H506-H515. doi: 10.1152/ajpheart.00473.2018. Epub 2018 Dec 14.


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.

Keywords: adipose tissue; hypertension; prorenin receptor; soluble prorenin receptor; vasopressin.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / drug effects*
  • Adipose Tissue / metabolism
  • Angiotensin II / blood
  • Angiotensin II Type 1 Receptor Blockers / pharmacology*
  • Angiotensinogen / genetics
  • Angiotensinogen / metabolism
  • Animals
  • Antihypertensive Agents / pharmacology*
  • Blood Pressure*
  • Female
  • Kidney / drug effects
  • Kidney / metabolism
  • Liver / drug effects
  • Liver / metabolism
  • Losartan / pharmacology*
  • Mice
  • Mice, Inbred C57BL
  • Prorenin Receptor
  • Receptors, Cell Surface / blood*
  • Receptors, Cell Surface / deficiency
  • Receptors, Cell Surface / genetics
  • Renin-Angiotensin System*
  • Vasopressins / pharmacology


  • Angiotensin II Type 1 Receptor Blockers
  • Antihypertensive Agents
  • Receptors, Cell Surface
  • Vasopressins
  • Angiotensinogen
  • Angiotensin II
  • Losartan
  • Prorenin Receptor