Neuronal and endothelial nitric oxide synthase expression in outer medullaof streptozotocin-induced diabetic rat kidney

Aims/hypothesis. Several investigations have shown that the renal medulla h as a greater capacity to generate nitric oxide than the renal cortex. To fu rther evaluate the changes of nitric oxide synthesis in the kidney, particu larly in the outer medulla, in disorders involving fluid and electrolyte im balances, we sought to determine renal nitric oxide synthase expression in the diabetic rats. Methods. We determined renal nitric oxide synthase mRNA and urinary nitrite /nitrate excretion in 12 normal and 12 streptozotocin-induced diabetic rats by reverse transcription-polymerase chain reaction with Southern blot hybr idization and with Griess reaction, respectively. Nitric oxide synthase imm unoreactivity was detected by immunohistochemistry in four normal and four diabetic rats. Results. Neuronal and endothelial nitric oxide synthase mRNA were 3.5-fold and 1.8-fold increased in the outer medulla of 12 diabetic rats with no dif ference found in the cortex and inner medulla when compared with 12 normal rats. Urinary nitrite/nitrate excretion was significantly increased from th e first week after diabetic induction. In normal rats, immunohistochemical studies showed positive neuronal and endothelial nitric oxide synthase immu nostaining in almost all segments of renal tubules. Diabetic rats had the g reatest enhancement of immunostaining for neuronal and endothelial nitric o xide synthase in the proximal straight tubule and medullary thick ascending limb. Conclusion/interpretation. Our results indicate that increases in neuronal and endothelial nitric oxide synthase synthesis in the kidney, particularly in the outer medulla, possibly play an important part in the adaptation of renal function to hyperglycaemia and hyperosmolality in diabetes.