Background: Neuronal nitric oxide synthase (nNOS) is abundant at macula densa in the juxtaglomerular apparatus of the kidney where it modulates tubuloglomerular feedback. Earlier studies in rats have demonstrated that selective long-term blockade of nNOS causes hypertension. The present study was performed using nNOS knock-out mice (nNOS-/-) to further clarify the role of nNOS in blood-pressure regulation.

Methods: Mean arterial blood-pressure (MAP) and heart rate (HR) was measured by telemetry, urinary electrolyte excretion was measured in metabolism cages and plasma renin concentration (PRC) by radioimmunoassay. All parameters were measured in unrestrained, conscious animals on low-, normal- and high sodium diets.

Results: No differences was found in MAP between nNOS-/- and controls on any diet. During daytime, the HR of nNOS-/- was significantly lower than controls on all diets. This was also found during nighttime, but only when data associated with activity was removed. PRC was not different between the genotypes on normal and high sodium diet, but the physiological increase in PRC when given low sodium diet was absent in nNOS-/-. Only on low sodium diet, the diuresis and osmolar excretion was found to be increased in nNOS-/-.

Conclusions: Our results show that nNOS-/- mice are normotensive within a wide range of sodium diets. The reduced heart rate could be caused by NO deficiency in the heart as nNOS is expressed in myocytes. Furthermore, nNOS-/- were unable to increase plasma renin during sodium restriction. Our results support earlier findings suggesting an important role of nNOS in regulation of renin release.