Role of nitric oxide in the control of glomerular microcirculation.

1. Nitric oxide (NO) plays an important role in the control of glomerular haemodynamics and is synthesized from the amino acid L-arginine by a family of enzymes, NO synthase (NOS). 2. Nitric oxide synthase is present in the endothelium and also in the macula densa, a plaque of specialized tubular epithelial cells. Endothelial NOS is known to be stimulated by shear stress and hormones, while the factor that regulates the activity of macula densa NOS remains undefined. 3. Studies with the in vitro microperfusion of glomerular arterioles have shown that the constriction of afferent arterioles (Af-Art) induced by myogenic responses and angiotensin II (AngII) is stronger in the absence rather than in the presence of luminal flow. Furthermore, endothelial disruption or NOS inhibition abolishes such differences, suggesting that flow through the lumen stimulates the endothelium to synthesize and release NO, which in turn attenuates both the myogenic response and the action of AngII in the Af-Art. 4. In contrast, NOS inhibitors have no effect on efferent arteriolar (Ef-Art) constriction induced by AngII. 5. In preparations in which Af-Art and the macula densa are simultaneously microperfused, selective inhibition of macula densa NOS has been shown to augment Af-Art constriction when the NaCl concentration at the macula densa is high, suggesting that the macula densa produces NO, which in turn modulates tubuloglomerular feedback. 6. Thus, the differential actions of NO in the Af-Art, Ef-Art and the macula densa may be important in the control of glomerular haemodynamics under various physiological and pathological conditions.