<p>The kidney is the major organ regulating the extracellular fluid volume and thereby the arterial blood pressure. The neuronal isoform of nitric oxide synthase (nNOS) in the kidney is predominantly located in the macula densa cells. These cells are sensors for both renin release and the tubuloglomerular feedback mechanism (TGF), which is an important regulator of the glomerular filtration rate and afferent arteriole tone. The aim of this investigation was to elucidate the function of nNOS in the macula densa cells.</p><p>Acute nNOS inhibition in rats resulted in an increased TGF responsiveness and unchanged blood pressure while, after chronic inhibition, the TGF was normalised and the blood pressure was elevated. The plasma renin concentration was elevated in rats on long-term low salt diet, but was not significantly affected by chronic nNOS inhibition. On the other hand, nNOS inhibition for four days increased plasma renin concentration in rats treated with a low salt diet. The renal vasculature of rats exhibits a diminished renal blood flow and intracellular Ca2+ response to angiotensin II after one week blockade of nNOS while angiotensin II’s effect on the renal blood flow was abolished after four weeks treatment. Acute extracellular volume expansion diminish the TGF sensitivity thus assisting the elimination of excess fluid but after acute addition of nNOS inhibitor to volume expanded rats the TGF sensitivity restored.</p><p>In conclusion, the results from the present study suggest an important role for nNOS in the macula densa cells in the regulation of the arterial blood pressure and the modulation of the TGF response.</p>

The kidney is the major organ regulating the extracellular fluid volume and thereby the arterial blood pressure. The neuronal isoform of nitric oxide synthase (nNOS) in the kidney is predominantly located in the macula densa cells. These cells are sensors for both renin release and the tubuloglomerular feedback mechanism (TGF), which is an important regulator of the glomerular filtration rate and afferent arteriole tone. The aim of this investigation was to elucidate the function of nNOS in the macula densa cells. Acute nNOS inhibition in rats resulted in an increased TGF responsiveness and unchanged blood pressure while, after chronic inhibition, the TGF was normalised and the blood pressure was elevated. The plasma renin concentration was elevated in rats on long-term low salt diet, but was not significantly affected by chronic nNOS inhibition. On the other hand, nNOS inhibition for four days increased plasma renin concentration in rats treated with a low salt diet. The renal vasculature of rats exhibits a diminished renal blood flow and intracellular Ca2+ response to angiotensin II after one week blockade of nNOS while angiotensin II’s effect on the renal blood flow was abolished after four weeks treatment. Acute extracellular volume expansion diminish the TGF sensitivity thus assisting the elimination of excess fluid but after acute addition of nNOS inhibitor to volume expanded rats the TGF sensitivity restored. In conclusion, the results from the present study suggest an important role for nNOS in the macula densa cells in the regulation of the arterial blood pressure and the modulation of the TGF response.