| First Author | Jia Z | Year | 2006 |
| Journal | Circ Res | Volume | 99 |
| Issue | 11 | Pages | 1243-51 |
| PubMed ID | 17095726 | Mgi Jnum | J:129057 |
| Mgi Id | MGI:3768592 | Doi | 10.1161/01.RES.0000251306.40546.08 |
| Citation | Jia Z, et al. (2006) Deletion of microsomal prostaglandin E synthase-1 increases sensitivity to salt loading and angiotensin II infusion. Circ Res 99(11):1243-51 |
| abstractText | 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 E(2) 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 E(2) release. These findings have revealed a mPGES-1/prostaglandin E(2)/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. |
