Blunted tubuloglomerular feedback by absence of angiotensin type 1A receptor involves neuronal NOS.

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Abstract
To define the role of angiotensin type 1A (AT 1A ) receptor in modulating tubuloglomerular feedback signals and to determine its relationship to neuronal NO synthase (nNOS), the diameter of the afferent arterioles of wild-type and AT 1A receptor–deficient mice was measured by the blood-perfused juxtamedullary nephron technique. The afferent arteriolar diameter of wild-type and AT 1A receptor–deficient mice averaged 16.7±0.6 (n=9) and 16.8±0.7 μm (n=9), respectively. In the wild-type mice, addition of 10 μmol/L acetazolamide to the blood perfusate exerted a biphasic afferent arteriolar constriction, with the initial response and sustained response averaging 47.2±3.8% and 33.9±3.3%, respectively. In AT 1A receptor–deficient mice, the initial response and sustained response averaged 51.6±3.6% and 9.5±1.3%, respectively, and the sustained response was significantly attenuated compared with that of wild-type mice. Inhibition of nNOS with 10 μmol/L S -methyl- l -thiocitrulline significantly decreased the afferent arteriolar diameter of AT 1A receptor–deficient mice, from 15.1±1.2 to 5.0±0.3 μm (n=7), and the decrease was significantly greater than that observed in wild-type mice (from 15.9±1.2 to 10.6±1.3 μm; n=8). During nNOS inhibition, the initial and sustained afferent arteriolar constrictor responses to acetazolamide in wild-type mice averaged 54.4±6.4% and 44.8±11.3%; respectively, and were similar to those in AT 1A receptor–deficient mice (53.2±6.4% and 59.5±4.4%, respectively). These results suggest that AT 1A receptors enhance tubuloglomerular feedback–mediated afferent arteriolar constriction, at least in part, through reducing the counteracting modulation by nNOS.

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