Role of prostaglandins in collecting duct-derived endothelin-1 regulation of blood pressure and water excretion

Oct 5, 2007American journal of physiology. Renal physiology

How prostaglandins influence blood pressure and water balance controlled by a kidney hormone

AI simplified

Circadian Biology on OpenScience ↗PubMed ↗DOI ↗

Abstract

Urinary PGE(2) excretion was unexpectedly increased in CD ET-1 knockout mice compared with controls during normal salt and water intake.

Salt loading significantly increased urinary PGE(2) excretion in both knockout and control mice, with higher levels observed in knockout animals.
Acute isolation of the inner medullary collecting duct from knockout mice showed increased PGE(2) production that was dependent on COX-2.
No increase in COX-2 protein or mRNA levels was detected in the inner medulla or inner medullary collecting duct of knockout mice.
Blood pressure was elevated in knockout mice on both normal and high-sodium diets compared to controls, unaffected by COX inhibitors indomethacin or NS-398.
Indomethacin or NS-398 treatment increased urine osmolality and reduced urine volume specifically in knockout mice, not in controls.

AI simplified

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.

Full Text

Full text is available at the source.

View full text ↗

Role of prostaglandins in collecting duct-derived endothelin-1 regulation of blood pressure and water excretion

Abstract

Full Text

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the circadian biology brief

Abstract

Full Text

Related papers

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the circadian biology brief