Renal medullary cyclooxygenase-2 and (pro)renin receptor expression during angiotensin II-Dependent hypertension

ALEXIS ANTONIO GONZALEZ PARRA, Torrance Green, Christina Luffman, Camille R.T. Bourgeois, L. Gabriel Navar, Minolfa C. Prieto

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

The (pro)renin receptor [(P)RR] upregulates cyclooxygenase-2 (COX-2) in inner medullary collecting duct (IMCD) cells through ERK1/2. Intrarenal COX-2 and (P)RR are upregulated during chronic ANG II infusion. However, the duration of COX-2 and (P)RR upregulation has not been determined. We hypothesized that during the early phase of ANG II-dependent hypertension, membrane-bound (P)RR and COX-2 are augmented in the renal medulla, serving to buffer the hypertensinogenic and vasoconstricting effects of ANG II. In Sprague-Dawley rats infused with ANG II (0.4 g·min-1·kg-1), systolic blood pressure (BP) increased by day 7 (162±5 vs. 114±10 mmHg) and continued to increase by day 14 (198±15 vs. 115±13 mmHg). Membrane-bound (P)RR was augmented at day 3 coincident with phospho-ERK1/2 levels, COX-2 expression, and PGE2 in the renal medulla. In contrast, membrane- bound (P)RR was reduced and COX-2 protein levels were not different from controls by day 14. In cultured IMCD cells, ANG II increased secretion of the soluble (P)RR. In anesthetized rats, COX-2 inhibition decreased the glomerular filtration rate (GFR) and renal blood flow (RBF) during the early phase of ANG II infusion without altering BP. However, at 14 days of ANG II infusions, COX-2 inhibition decreased mean arterial BP (MABP), RBF, and GFR. Thus, during the early phase of ANG II-dependent hypertension, the increased (P)RR and COX-2 expression in the renal medulla may contribute to attenuate the vasoconstrictor effects of ANG II on renal hemodynamics. In contrast, at 14 days the reductions in RBF and GFR caused by COX-2 inhibition paralleled the reduced MABP, suggesting that vasoconstrictor COX-2 metabolites contribute to ANG II hypertension.

Original languageEnglish
Pages (from-to)F962-F970
JournalAmerican Journal of Physiology - Renal Physiology
Volume307
Issue number8
DOIs
StatePublished - 15 Oct 2014

Keywords

  • Arterial blood pressure
  • Collecting duct
  • Glomerular filtration rate
  • MAP kinases
  • Prostaglandin E
  • Renal blood flow

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