Collecting duct-specific knockout of endothelin-1 causes hypertension and sodium retention.

Collecting duct-specific knockout of the endothelin B receptor causes hypertension and sodium retention.

Collecting duct (CD)-derived endothelin-1 (ET-1) inhibits renal Na reabsorption and its deficiency increases blood pressure (BP). The role of CD endothelin B (ETB) receptors in mediating these effects is unknown. CD-specific knockout of the ETB receptor was achieved using an aquaporin-2 promoter-Cre recombinase transgene and the loxP-flanked ETB receptor gene (CD ETB KO). Systolic BP in mice wi...

Explorer Combined knockout of collecting duct endothelin A and B receptors causes hypertension and sodium retention

Combined knockout of collecting duct endothelin A and B receptors causes hypertension and sodium retention.

The collecting duct (CD) endothelin (ET) system regulates blood pressure (BP) and Na excretion. CD-specific knockout (KO) of ET-1 causes hypertension, CD-specific KO of the ETA receptor does not alter BP, while CD-specific KO of the ETB receptor increases BP to a lesser extent than CD ET-1 KO. These findings suggest a paracrine role for CD-derived ET-1; however, they do not exclude compensation...

Collecting duct-derived endothelin regulates arterial pressure and Na excretion via nitric oxide.

Mice with a collecting duct-specific deletion of endothelin-1 are hypertensive and have impaired Na excretion. Because endothelin-1 activates NO synthase (NOS) in the collecting duct, we hypothesized that impaired renal NO production in knockout mice exacerbates the hypertensive state. Control and knockout mice were treated chronically with N(G)-nitro-l-arginine methyl ester, and blood pressure...

Physiological actions of renal collecting duct endothelin.

THE CONTRIBUTION OF ENDOTHELIN to regulation of renal function under normal physiological conditions is unclear. Many cells in the kidney produce endothelin (9). Endothelin has been reported to have effects that both promote (2, 3, 5–7, 12–14, 16, 18) and reduce (2, 8, 13, 15) urinary sodium excretion and urinary volume. This may be due to the fact that endothelin exerts its effects via two rec...