Faculty Collaboration Database

Chronic administration of nitric oxide reduces angiotensin II receptor type 1 expression and aldosterone synthesis in zona glomerulosa cells. Am J Physiol Endocrinol Metab 2004 Nov;287(5):E820-7

Date

06/17/2004

Pubmed ID

15198935

DOI

10.1152/ajpendo.00183.2004

Scopus ID

2-s2.0-6044274619 (requires institutional sign-in at Scopus site)   11 Citations

Abstract

Acute nitric oxide (NO) inhibits angiotensin II (ANG II)-stimulated aldosterone synthesis in zona glomerulosa (ZG) cells. In this study, we investigated the effects of chronic administration of NO on the ANG II receptor type 1 (AT1) expression and aldosterone synthesis. ZG cells were treated daily with DETA NONOate (10(-4) M), an NO donor, for 0, 12, 24, 48, 72, and 96 h. Chinese hamster ovary (CHO) cells, stably transfected with the AT1B receptor, were used as a positive control. Western blot analysis indicated that AT1 receptor expression was decreased as a function of time of NO administration in both CHO and ZG cells. ANG II binding to its receptors was determined by radioligand binding. NO treatment of ZG cells for 96 h resulted in a decrease in ANG II binding compared with control. The receptor density was decreased to 1,864 +/- 129 fmol/mg protein from 3,157 +/- 220 fmol/mg protein (P < 0.005), but the affinity was not changed (1.95 +/- 0.22 vs. 1.88 +/- 0.21 nM). Confocal Raman microspectroscopy and immunocytochemistry both confirmed that the expression of AT1 receptors in ZG cells decreased with chronic NO administration. In addition, chronic NO administration also decreased the expression of cholesterol side-chain cleavage enzyme in ZG cells and inhibited ANG II- and 25-hydroxycholesterol-stimulated aldosterone synthesis in ZG cells. This study demonstrates that chronic administration of NO inhibits aldosterone synthesis in ZG cells by downregulation of the expression of both AT1 receptors and cholesterol side-chain cleavage enzyme.

Author List

Nithipatikom K, Holmes BB, McCoy MJ, Hillard CJ, Campbell WB

Authors

William B. Campbell PhD Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin
Cecilia J. Hillard PhD Associate Dean, Center Director, Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin

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

Aldosterone
Angiotensin II
Animals
Blotting, Western
CHO Cells
Cattle
Cells, Cultured
Cholesterol Side-Chain Cleavage Enzyme
Cricetinae
Cricetulus
Dose-Response Relationship, Drug
Down-Regulation
Drug Administration Schedule
Humans
Immunohistochemistry
Nitric Oxide
Receptor, Angiotensin, Type 1
Spectrum Analysis, Raman
Zona Glomerulosa