Nitric oxide inhibits ADH-stimulated osmotic water permeability in cortical collecting ducts

Nitric oxide (NO) reduces blood pressure in vivo by two mechanisms, vasodilation and increasing urinary volume; however, the exact mechanism by which it increases urinary volume is not clear. We hypothesized that NO inhibits antidiuretic hormone (ADH)-stimulated fluid reabsorption (J(v)) by the isolated rat cortical collecting duct (CCD) by decreasing water permeability (P-f) and sodium reabsorption (J(Na)) In the presence of 10(-11) MADH, J(v) was 0.15 +/- 0.04 nl . min(-1). mm(-1); after 10(-6) M spermine nonoate (SPM) was added to the bath, J(v) decreased to 0.06 +/- 0.03 nl . min(-1). mm(-1) (P < 0.03). To investigate whether the inhibition of J(v) was the result of decreased P-f and/or J(Na), we first tested the effect of SPM on ADH-stimulated P-f. Basal P-f was stimulated to 289.2 +/- 77.3 mu m/s after 10(-11) MADH was added to the bath (P < 0.01). SPM decreased P-f to 159.8 +/- 45.0 mu m/s (P < 0.05). To ensure that this effect on P-f was due to NO release, we used another NO donor, nitroglycerin (NTG). P-f was initially -25.8 +/- 18.3 mu m/s and increased to 133.9 +/- 30.5 mu m/s after addition of 10(-11) MADH (P < 0.002). NTG, 20 mu M, lowered P-f to 92.4 +/- 18.4 mu m/s (P < 0.02). In the presence of 10(-9) MADH, NTG also decreased P-f (P < 0.04). Next we investigated the effect of SPM on ADH-stimulated J(Na). In the presence of ADH, J(Na) was 37.8 +/- 7.3 pmol . min(-1). mm(-1). After SPM was added, it dropped to 24.3 +/- 5.1 pmol . min(-1). mm(-1) (P < 0.05). Time controls exhibited no change in ADH-stimulated J(v), P-f, or J(Na). We concluded that 1) NO decreases ADH-stimulated water and sodium transport in the isolated CCD, and 2) water reabsorption is inhibited by a primary effect on P-f. A direct effect of NO on the CCD may explain its natriuretic and diuretic effects observed in vivo.