The Role of Nitric Oxide in the Urine Concentration Mechanism in Diabetic Rats

Abstract

Diabetes mellitus (DM) results in osmotic diuresis and lowered levels of nitric oxide (NO). We examined how absence of NO affects transporters involved in urine concentration in DM. Sprague Dawley rats were injected with streptozotocin to induce DM. Control and DM rats were given L‐NAME, a non‐selective inhibitor of nitric oxide synthase. Urine osmolality was lower in DM rats, however in L‐NAME treated DM rats levels were similar to untreated and L‐NAME treated animals. L‐NAME treatment did not change urine output however L‐NAME treated DM rats produced less urine than untreated DM rats. UT‐A1 was increased in DM animals. L‐NAME treatment alone did not alter UT‐A1 abundance however DM‐treated rats had increased UT‐A1 expression but the abundance was less than untreated‐DM animals. AQP2 abundance was up both DM and DM‐L‐NAME rats compared to the control group. L‐NAME treatment had no effect on control or DM rat AQP2 expression. Similarly, NKCC2 expression was increased in both DM and DM‐L‐NAME rat. L‐NAME did not alter NKCC2 abundance compared to control or the DM untreated animal. Increased protein expression of UT‐A1, AQP2 and NKCC2 observed in DM rats provides a compensatory mechanism however lack of NO prevents the increase of UT‐A1 in DM but reduces urine osmolality and output. Data suggest that alteration of NO levels may be beneficial in treatment of polyuria occurring in DM.