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(Hypertension. 2000;35:324.)
© 2000 American Heart Association, Inc.

Scientific Contributions

Inhibition of Adrenal Cell Aldosterone Synthesis by Endogenous Nitric Oxide Release

Craig J. Hanke; Timothy O’Brien; Kirkwood A. Pritchard, Jr; William B. Campbell

From the Department of Pharmacology and Toxicology (C.J.H., K.A.P., W.B.C.), Medical College of Wisconsin, Milwaukee, Wis; and Division of Endocrinology (T.O.), Mayo Clinic, Rochester, Minn.

Correspondence to William B. Campbell, PhD, Medical College of Wisconsin, Department of Pharmacology and Toxicology, 8701 Watertown Plank Rd, Milwaukee, WI 53226. E-mail wbcamp{at}mcw.edu

Abstract—Adrenal zona glomerulosa (ZG) cells do not contain nitric oxide (NO) synthase (NOS). We conferred endothelial NOS activity onto adrenal ZG cells through transduction with a recombinant adenovirus encoding the endothelial NOS gene (AdeNOS) to determine the effect of endogenous NO on aldosterone synthesis. A 135-kDa protein band immunoreactive to anti–endothelial NOS antibody was observed in Western blots of AdeNOS-transduced ZG cells but not in control cells or cells transduced with adenovirus encoding the ß-galactosidase gene (AdßGal). Nitrate/nitrite production in AdeNOS-transduced ZG cells increased from 0.15±0.01 to 0.27±0.01 µmol/L after stimulation with 1 nmol/L angiotensin II. The treatment of AdeNOS-transduced cells with 30 µmol/L L-nitro-arginine decreased angiotensin II–stimulated nitrite production from 0.27±0.01 to 0.17±0.01 µmol/L. Basal and angiotensin II–stimulated nitrite production was not increased in AdßGal-transduced or control cells. AdeNOS-transduced cells demonstrated diaminofluorescein-2 diacetate fluorescence, which was blocked by pretreatment with L-nitro-arginine. Angiotensin II–stimulated aldosterone synthesis decreased from 5123±177 pg/mL in AdßGal-transduced ZG cells to 72±27 pg/mL in AdeNOS-transduced cells. Treatment with the NOS inhibitor thiocitrulline (30 µmol/L) increased angiotensin II–stimulated aldosterone synthesis to 2158±45 pg/mL after AdeNOS transduction. These data demonstrate that adenovirus-mediated gene transfer of eNOS in ZG cells results in the expression of active endothelial NOS enzyme and that this endogenous NO production by ZG cells decreases aldosterone synthesis.

Key Words: nitric oxide • aldosterone • adrenal glands • adenovirus • nitric oxide synthase • zona glomerulosa

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