| First Author | Ge Y | Year | 2007 |
| Journal | Am J Physiol Renal Physiol | Volume | 293 |
| Issue | 6 | Pages | F1805-10 |
| PubMed ID | 17913832 | Mgi Jnum | J:145100 |
| Mgi Id | MGI:3833505 | Doi | 10.1152/ajprenal.00307.2007 |
| Citation | Ge Y, et al. (2007) Role of prostaglandins in collecting duct-derived endothelin-1 regulation of blood pressure and water excretion. Am J Physiol Renal Physiol 293(6):F1805-10 |
| abstractText | Collecting duct (CD)-derived endothelin-1 (ET-1) exerts natriuretic, diuretic, and hypotensive effects. In vitro studies have implicated cyclooxygenase (COX) metabolites, and particularly PGE(2), as important mediators of CD ET-1 effects. However, it is unknown whether PGE(2) mediates CD-derived ET-1 actions in vivo. To test this, CD ET-1 knockout (KO) and control mice were studied. During normal salt and water intake, urinary PGE(2) excretion was unexpectedly increased in CD ET-1 KO mice compared with controls. Salt loading markedly increased urinary PGE(2) excretion in both groups of mice; however, the levels remained relatively higher in KO animals. Acutely isolated inner medullary collecting duct (IMCD) from KO mice also had increased PGE(2) production. The increased IMCD PGE(2) was COX-2 dependent, since NS-398 blocked all PGE(2) production. However, increased CD ET-1 KO COX-2 protein or mRNA could not be detected in inner medulla or IMCD, respectively. Inner medullary COX-1 mRNA and protein levels and IMCD COX-1 mRNA levels were unaffected by Na intake or CD ET-1 KO. KO mice on a normal or high-Na diet had elevated blood pressure compared with controls; this difference was not altered by indomethacin or NS-398 treatment. However, indomethacin or NS-398 did increase urine osmolality and reduce urine volume in KO, but not control, animals. In summary, IMCD COX-2-dependent PGE(2) production is increased in CD ET-1 KO mice, indicating that CD-derived ET-1 is not a primary regulator of IMCD PGE(2). Furthermore, the increased PGE(2) in CD ET-1 KO mice partly compensates for loss of ET-1 with respect to maintaining urinary water excretion, but not in blood pressure control. |
