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(Hypertension. 1996;27:679-683.)
© 1996 American Heart Association, Inc.
Articles |
From the Division of Hypertension and Vascular Research, Henry Ford Hospital, Detroit, Mich.
Correspondence to Jeffrey L. Garvin, Division of Hypertension and Vascular Research, Henry Ford Hospital, 2799 W Grand Blvd, Detroit, MI 48202.
Abstract Nitric oxide has a diuretic effect in vivo. We have shown that nitric oxide inhibits antidiuretic hormonestimulated osmotic water permeability in the collecting duct; however, the mechanism by which this occurs is unknown. We hypothesized that inhibition of antidiuretic hormonestimulated water permeability by nitric oxide in the collecting duct is the result of activation of cGMP-dependent protein kinase, which in turn decreases intracellular cAMP. To test this hypothesis, we microperfused cortical collecting ducts. Antidiuretic hormonestimulated water permeability was 317±47 µm/s (P<.001). Addition of spermine NONOate, a nitric oxide donor, to the bath decreased water permeability to 74±38 µm/s (P<.002). In the presence of LY 83583, an inhibitor of soluble guanylate cyclase, spermine NONOate did not change water permeability. Addition of spermine NONOate increased cGMP production (P<.01). In the presence of the cGMP-dependent protein kinase inhibitor, spermine NONOate did not change water permeability. Since antidiuretic hormone increases water permeability by increasing cAMP, we hypothesized that nitric oxide inhibits water permeability by decreasing cAMP. In tubules pretreated with antidiuretic hormone, intracellular cAMP was 18.9±3.9 fmol/mm. In tubules treated with antidiuretic hormone and spermine NONOate, cAMP was 9.3±1.7 fmol/mm (P<.03). We also examined the effect of spermine NONOate on dibutyryl-cAMPstimulated water permeability. In the presence of dibutyryl-cAMP, water permeability was 388±30 µm/s. Addition of spermine NONOate had no significant effect on water permeability. Time controls and inhibitors by themselves did not change antidiuretic hormonestimulated water permeability. We concluded that nitric oxide decreases antidiuretic hormonestimulated water permeability by increasing cGMP via soluble guanylate cyclase, activating cGMP-dependent protein kinase and decreasing cAMP.
Key Words: nitric oxide vasopressin cGMP protein kinases cAMP
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