Kidney function follows a 24-h rhythm subject to regulation by circadian genes including the transcription factor. A high-salt diet induces a phase shift inexpression in the renal inner medulla that is dependent on endothelin type B (ET) receptors. Furthermore, ETreceptor-mediated natriuresis is sex dependent. Therefore, experiments tested the hypothesis that collecting ductregulates blood pressure in a sex-dependent manner. We generated a mouse model that lacksexpression in the collecting duct, where ETreceptor abundance is highest. Male, but not female, collecting ductknockout (CDBmal1KO) mice had significantly lower 24-h mean arterial pressure (MAP) than flox controls (105 ± 2 vs. 112 ± 3 mmHg for male mice and 106 ± 1 vs. 108 ± 1 mmHg for female mice, by telemetry). After 6 days on a high-salt (4% NaCl) diet, MAP remained significantly lower in male CDBmal1KO mice than in male flox control mice (107 ± 2 vs. 113 ± 1 mmHg), with no significant differences between genotypes in female mice (108 ± 2 vs. 109 ± 1 mmHg). ETreceptor blockade for another 6 days increased MAP similarly in both male and female CDBmal1KO and flox control mice. However, MAP remained lower in male CDBmal1KO mice than in male flox control mice (124 ± 2 vs. 130 ± 2 mmHg). No significant differences were observed between female CDBmal1KO and flox mice during ETblockade (130 ± 2 vs. 127 ± 2 mmHg). There were no significant genotype differences in amplitude or phase of MAP in either sex. These data suggest that collecting ducthas no role in circadian MAP but plays an important role in overall blood pressure in male, but not female, mice. Bmal1Bmal1Bmal1Bmal1Bmal1Bmal1B B B B B
