Abstract
There is evidence that nitric oxide, an endothelium-derived relaxing factor, may be produced by the macula densa, as well as by blood vessels, within the kidney. To examine the role of nitric oxide in macula densa control of glomerular hemodynamics directly, we performed in vitro microperfusions of both rabbit afferent arterioles (with the glomerulus intact) and adherent tubular segments consisting of portions of the thick ascending limb, macula densa, and early distal tubule. While keeping afferent arteriolar pressure constant at 60 mmHg, we examined the effect of Nw-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthesis, added to a macula densa perfusate. When the macula densa perfusate was changed from low to high NaCl, the diameter of the arterioles decreased from 16.3 +/- 1.0 to 14.0 +/- 1.1 microns (n = 10; P < 0.001). Addition of 10(-5) M L-NAME to the high NaCl solution further decreased the diameter to 11.9 +/- 1.1 microns (P < 0.001). In contrast, when macula densa perfusion was maintained with the low NaCl solution, addition of L-NAME had no effect. L-NAME-induced constriction was completely reversed by adding 10(-3) M L-arginine (the precursor of nitric oxide) but not D-arginine (an inactive isomer) to the macula densa perfusate. We confirmed that perfusing the macula densa with L-NAME did not affect the vasodilator action of acetylcholine added to the lumen of the afferent arteriole, indicating that NO synthesis by the arteriole was not altered. Thus, our findings suggest that the macula densa may produce nitric oxide, which in turn modulates the afferent arteriolar constriction induced by high concentrations of NaCl at the macula densa.
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