Increased severity of renal impairment in nephritic mice lacking the EP1 receptor.

Abstract

In experimental glomerulonephritis, inhibition of renal prostaglandin (PG) synthesis by nonsteroidal-anti-inflammatory drugs (NSAIDs) moderates proteinuria, yet can induce harmful effects on renal blood flow and Na+ - K+ - water balance thereby implicating 1 or more prostanoid receptor subtypes. We investigated the role of the PGE2 EP1 receptor in nephritis since it is expressed in the glomerulus, collecting duct and vasculature in which its activity might contribute to adaptive or maladaptive responses. Accordingly, a mouse model of accelerated antiglomerular basement membrane (anti-GBM) nephrotoxic serum (NTS) nephritis was induced in mice with targeted-deletion of the EP1 receptor (EP1-/-). Proteinuria was similar between wild-type (wt) and EP1-/- NTS groups, thus negating a role for this subtype in modulating the glomerular permeability barrier in this model of anti-GBM NTS. However, overall renal damage was more acute in NTS EP1-/- mice, as evidenced by the degree of glomerular mesangial matrix expansion and the frequency of tubular dilatations. These changes in renal pathology were accompanied by stronger impairment of renal function in NTS EP1-/- mice, such that levels of serum creatinine, urea, Na+, and K+ were each significantly higher than those observed in NTS wt mice. Lastly, compared with wt mice, induction of NTS more severely reduced urine osmolality and body mass in EP1-/- mice. Taken together, the increased renal impairment seen in NTS EP1-/- mice suggests that the EP1 subtype plays a compensatory role in the context of acute nephritis.

• Authors: Sherine Rahal, Lyne I McVeigh, Yahua Zhang, Youfei Guan, Matthew D Breyer, Chris R J Kennedy
• Journal: Canadian journal of physiology and pharmacology (Can J Physiol Pharmacol) 2006 Aug-Sep Vol. 84 Issue 8-9 Pg. 877-85 ISSN: 0008-4212 [Print] Canada
• PMID: 17111032 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies
• Immune Sera
• Ptger1 protein, mouse
• Receptors, Prostaglandin E
• Receptors, Prostaglandin E, EP1 Subtype
• Aldosterone
• Urea
• Creatinine
• Potassium

Topics

• Albuminuria (etiology)
• Aldosterone (blood)
• Animals
• Antibodies (immunology)
• Creatinine (blood)
• Female
• Glomerular Basement Membrane (immunology)
• Glomerulonephritis (complications, pathology, physiopathology)
• Immune Sera (immunology)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Potassium (blood)
• Receptors, Prostaglandin E (deficiency, genetics, metabolism)
• Receptors, Prostaglandin E, EP1 Subtype
• Urea (blood)