Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2018 Nov;470(11):1691-1703.
doi: 10.1007/s00424-018-2183-3. Epub 2018 Jul 19.

The renal vasodilatory effect of prostaglandins is ameliorated in isolated-perfused kidneys of endotoxemic mice

Manuel Meurer  1 , Katharina Ebert  2 , Frank Schweda  3 , Klaus Höcherl  4
Affiliations

The renal vasodilatory effect of prostaglandins is ameliorated in isolated-perfused kidneys of endotoxemic mice

Manuel Meurer et al. Pflugers Arch. 2018 Nov.

Abstract

Endotoxemia-related acute kidney injury (AKI) is associated with increased formation of prostaglandins, which may serve as a compensatory mechanism to maintain renal function. We hypothesized that an increase of renal EP2 or EP4 receptors and/or a downregulation of renal EP1 and EP3 receptors enhances PGE2-induced renal vasodilatation. Injection of lipopolysaccharide (LPS; 3 mg/kg i.p.) increased microsomal prostaglandin E synthase (mPGES)-1 and prostacyclin synthase expression, whereas mPGES-2 expression was unaltered. Further, LPS increased the mRNA abundance for the prostaglandin EP4 receptor, whereas the expressions of the EP1 and EP3 receptors were decreased. In isolated-perfused kidneys from control mice, PGE2 exerted a dual effect on renal vascular tone, inducing vasodilatation at lower concentrations and vasoconstriction at higher concentrations. In kidneys from endotoxemic mice, the vasodilatory component was more pronounced, whereas the vasoconstriction at higher PGE2 concentrations was absent. Similarly, prostacyclin (PGI2)-induced vasodilatation was more pronounced in endotoxemic kidneys. The enhanced vasodilatory effect was paralleled by an increase in renal vascular EP4 and prostacyclin IP receptor mRNA expression. Further, stimulation of renin secretion rate by PGE2 and PGI2 was enhanced in endotoxemic kidneys. Pretreatment with the cyclooxygenase (COX)-2 inhibitor SC-236 (10 mg/kg) did not alter the basal GFR, but augmented the LPS-induced decline in GFR, and attenuated the LPS-induced increase in plasma renin concentration in vivo. Our data suggest that an activation of the COX-2/mPGES-1 synthetic pathway is responsible for the increased renal formation of PGE2 in response to LPS and that the vasodilatory effect of PGE2 and PGI2 is enhanced during endotoxemia.

Keywords: Cyclooxygenase; Endotoxemia; Prostacyclin; Prostaglandin; Renal vascular tone; Renin.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

References

    1. N Engl J Med. 1984 Feb 2;310(5):279-83 - PubMed
    1. Circ Res. 1979 Jun;44(6):796-9 - PubMed
    1. Crit Care. 2018 Feb 27;22(1):52 - PubMed
    1. Endocrinology. 1980 May;106(5):1400-4 - PubMed
    1. Contrib Nephrol. 2010;167:14-24 - PubMed

Publication types

LinkOut - more resources