High blood glucose and osmolality, but not high urinary glucose and osmolality, affect neuronal nitric oxide synthase expression in diabetic rat kidney

We recently demonstrated that neuronal nitric oxide synthase (nNOS) messenger RNA (mRNA) is markedly increased in the kidneys of diabetic rats and water-deprived rats. It can be inferred that high plasma glucose and osmolality and high renal tubular glucose and osmolality are somehow involving in renal NOS synthesis in diabetic rats. Phlorizin, a competitive inhibitor of glucose transport in the proximal tubule, causes renal glycosuria in nondiabetic rats and reverses hyperglycemia in diabetic rats. To further investigate whether high plasma glucose and osmolality or high renal tubular glucose and osmolality influence renal NOS synthesis in diabetic rats, we measured nNOS mRNA levels in phlorizin-treated normal and diabetic rats. Neuronal NOS mRNA expression in the kidneys was not significantly different between normal rats and phlorizin-treated normal rats with high urinary glucose and osmolality. The phlorizin-treated diabetic rats showed a significant decrease in the ratio of nNOS to beta-actin mRNA compared with diabetic rats. On linear-regression analysis, plasma glucose was strongly positively correlated with nNOS mRNA expression in the cortex, outer medulla, and inner medulla (r(2) = .378, r(2) = .680, and r(2) = .445, respectively) of rat kidneys. Neither urine glucose concentration nor urine osmolality was correlated with nNOS mRNA expression in rat kidneys. In conclusion, our results indicate that nNOS mRNA expression in the kidneys of diabetic rats is directly affected by high blood glucose/osmolality but not by high urinary glucose or osmolality.