Rats and mice with hydronephrosis develop renal injury and hypertension. Furthermore, the tubuloglomerular feedback (TGF) is reset to higher sensitivity in the hydronephrotic kidney. Regulation of TGF- sensitivity is coupled to nitric oxide (NO) in the macula densa cells. We investigated if reduced NO availability is involved in the development of hypertension in hydronephrosis. Hydronephrosis was induced by ureteral obstruction in young spell outSD -rats. In the adult animals, blood pressure was measured telemetrically under different sodium conditions and before and after chronic administration of the NO-synthase inhibitor L-NAME or L- arginine (L-Arg). TGF-characteristics were determined by stop-flow pressure technique before and after administration of 7-NI or L-Arg. All hydronephrotic animals developed salt-sensitive hypertension. The blood pressure response to L-NAME treatment was more pronounced in controls than in hydronephrotic animals. L- Arg administration decreased blood pressure in hydronephrotic animals but not in the controls. During control conditions, reactivity of the TGF-response, as indicated by the maximal change in stop-flow pressure, was greater in the hydronephrotic group (14.4±1.0mmHg) compared to controls (9.4±0.8mmHg). The turning point (TP) was lower, indicating an increased sensitivity, in the hydronephrotic animals (14.9±1.4nl/min) than in the controls (19.1±1.2nl/min). 7-NI administration increased TGF-reactivity and sensitivity in control animals, whereas in hydronephrotic animals, NO synthase inhibition had no effect. L-Arg attenuated TGF-response to a greater extent in hydronephrotic kidneys than in controls. In hydronephrosis, reduced NO availability in the diseased kidney and subsequent resetting of the TGF-mechanism could play an important role in the development of salt-sensitive hypertension.