Nitric oxide in the juxtaglomerular apparatus plays an important role in controlling the tubuloglomerular feedback mechanism (TGF) and renin release. A continous production of NO in the macula densa cells is necessary to reduce the sensitivity of the TGF to prevent fluid volume retension and an overproduction of renin. In situations where macula densa cell NO concentration is reduced, fluid volume retension occurs and hypertension develops. This occurs in rats long-term treated with the nNOS inhibitor 7NI and also in rats that spontaneously develops hypertension such as the Milan Hypertensive strain (MHS) or spontaneously hypertensive rats (SHR). In particular, macula densa cell NO is an important factor to control the sensitivity of the TGF in a situation with volume expansion when renin production is reduced. In volume expansion TGF sensitivity is reduced to a low level but can be normalized or even sensitised during treatment with 7NI leading to a reduced GFR. In conclusion the actual NO concentration in the macula densa cells is an important factor to control the sensitivity of the TGF mechanism and also for the release of renin. Decreased NO concentration acts to increase TGF sensitivity leading to decreased GFR and fluid volume excretion and in addition to an incresed renin release. Macula densa cell NO concentration is therefore an important factor to determine arterial blood pressure through changes in fluid volume balance.