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Inhibition of adrenal cell aldosterone synthesis by endogenous nitric oxide release. Hypertension 2000 Jan;35(1 Pt 2):324-8

Date

01/21/2000

Pubmed ID

10642319

DOI

10.1161/01.hyp.35.1.324

Scopus ID

2-s2.0-0033972062   33 Citations

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 beta-galactosidase gene (AdbetaGal). Nitrate/nitrite production in AdeNOS-transduced ZG cells increased from 0.15+/-0.01 to 0.27+/-0.01 micromol/L after stimulation with 1 nmol/L angiotensin II. The treatment of AdeNOS-transduced cells with 30 micromol/L L-nitro-arginine decreased angiotensin II-stimulated nitrite production from 0.27+/-0. 01 to 0.17+/-0.01 micromol/L. Basal and angiotensin II-stimulated nitrite production was not increased in AdbetaGal-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 AdbetaGal-transduced ZG cells to 72+/-27 pg/mL in AdeNOS-transduced cells. Treatment with the NOS inhibitor thiocitrulline (30 micromol/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.

Author List

Hanke CJ, O'Brien T, Pritchard KA Jr, Campbell WB

Authors

William B. Campbell PhD Chair, Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin
Craig J. Hanke PhD Assistant Dean, Associate Professor in the Medical School Regional Campuses department at Medical College of Wisconsin
Kirkwood A. Pritchard PhD Professor in the Surgery department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Adenoviridae
Adenoviridae Infections
Aldosterone
Animals
Blotting, Western
Cattle
Cells, Cultured
Fluoresceins
Gene Expression Regulation, Enzymologic
Gene Transfer Techniques
Nitrates
Nitric Oxide
Nitric Oxide Synthase
Nitric Oxide Synthase Type III
Nitrites
Zona Glomerulosa
jenkins-FCD Prod-482 91ad8a360b6da540234915ea01ff80e38bfdb40a