Deletion of microsomal prostaglandin E synthase-1 increases sensitivity to salt loading and angiotensin II infusion

Zhanjun Jia, Aihua Zhang, Hui Zhang, Zheng Dong, Tianxin Yang

Research output: Contribution to journalArticle

81 Scopus citations

Abstract

Microsomal prostaglandin E synthase-1 (mPGES-1), a membrane-associated protein, is critically involved in the inflammatory response and may be involved in physiological processes as well. The present study examined the role of mPGES-1 in regulation of sodium balance and blood pressure in the settings of salt loading and angiotensin II infusion. mPGES-1 -/- mice developed severe and progressive hypertension associated with an inappropriate increase in sodium balance when fed a high-salt diet. These mice exhibited a significantly impaired ability to excrete an acute enteral load of NaCl. Under these 2 settings of salt loading, urinary excretion of prostaglandin E2 and nitrate/nitrite were remarkably increased in wild-type animals but not in mPGES-1 -/- mice. The changes of urinary cGMP paralleled that of urinary nitrate/nitrite. mPGES-1 -/- mice exhibited a remarkable inhibition of high salt-induced increase in gene expression of all 3 NO synthase isoforms, whereas these mice had upregulated expression of NO synthase III but not NO synthase I and NO synthase II at basal state. Chronic salt loading remarkably induced mPGES-1 protein expression exclusively in the distal nephron. In primary cultures of CD cells, mPGES-1 expression was significantly increased following exposure to hypertonic NaCl, in parallel with increased prostaglandin E2 release. These findings have revealed a mPGES-1/prostaglandin E2/NO/cGMP pathway that appears to be critically important for salt adaptation. In addition, we provide evidence that mPGES-1 deficiency sensitized the hypertensive effect of angiotensin II. Overall, this study has characterized the natriuretic and antihypertensive role of mPGES-1 that likely contributes to blood pressure homeostasis.

Original languageEnglish (US)
Pages (from-to)1243-1251
Number of pages9
JournalCirculation research
Volume99
Issue number11
DOIs
StatePublished - Nov 1 2006

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Keywords

  • Angiotensin II
  • Collecting duct
  • Mean arterial pressure
  • Nitric oxide
  • Prostaglandin E
  • mPGES-1

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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