Male, 22-week-old, db/db mice do not develop salt sensitivity but have impaired sodium handling and inflammation. (A) Female and (B) male 18-week-old db/db and db/+ mice were exposed to an HS diet for 4 weeks. MAP was continuously monitored by radiotelemetry. Data are expressed as daily average. At the end of the experiment (week 22), mice were housed in metabolic cages for 24-hour urine collection. (C) Urinary albumin was measured by ELISA in 24-hour urine and expressed as micrograms of albumin per milligram of creatinine. Data are expressed as dot plots. Horizontal bars represent the mean±SD. For saline test, (D) female and (E) male mice were challenged with an i.p. bolus of warmed saline, equivalent to 10% of their body weight, and placed in metabolic cages for hourly urine collection. Plots represent the accumulated excretion of sodium over a 5-hour collection period. n=6 per group. **P<0.01 by t test. (F) IL-1β, (G) IL-6, and (H) TNFα were evaluated in total kidney homogenates by ELISA. Data are expressed as dot plots. Horizontal bars represent the mean±SD (n=6 per group). *P<0.05, **P<0.01, ***P<0.001 by three-way ANOVA.