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Angiotensin II regulates adrenal vascular tone through zona glomerulosa cell-derived EETs and DHETs. Hypertension 2011 Feb;57(2):323-9

Date

01/05/2011

Pubmed ID

21199991

Pubmed Central ID

PMC3034648

DOI

10.1161/HYPERTENSIONAHA.110.158311

Scopus ID

2-s2.0-79551496438   15 Citations

Abstract

Elevated concentrations of aldosterone are associated with several cardiovascular diseases. Angiotensin II (Ang II) increases aldosterone secretion and adrenal blood flow. This concurrent increase in steroidogenesis and adrenal blood flow is not understood. We investigated the role of zona glomerulosa (ZG) cells in the regulation of vascular tone of bovine adrenal cortical arteries by Ang II. ZG cells enhanced endothelium-dependent relaxations to Ang II. The ZG cell-dependent relaxations to Ang II were unchanged by removing the endothelium-dependent response to Ang II. These ZG cell-mediated relaxations were ablated by cytochrome P450 inhibition, epoxyeicosatrienoic acid (EET) antagonism, and potassium channel blockade. Analysis of ZG cell EET production by liquid chromatography/mass spectrometry demonstrated an increase in EETs and dihydroxyeicosatrienoic acids with Ang II stimulation. These EETs and dihydroxyeicosatrienoic acids produced similar concentration-dependent relaxations of adrenal arteries, which were attenuated by EET antagonism. Whole-cell potassium currents of adrenal artery smooth muscle cells were increased by Ang II stimulation in the presence of ZG cells but decreased in the absence of ZG cells. This increase in potassium current was abolished by iberiotoxin. Similarly, 14,15-EET induced concentration-dependent increases in potassium current, which was abolished by iberiotoxin. ZG cell aldosterone release was not directly altered by EETs. These data suggest that Ang II stimulates ZG cells to release EETs and dihydroxyeicosatrienoic acids, resulting in potassium channel activation and relaxation of adrenal arteries. This provides a mechanism by which Ang II concurrently increases adrenal blood flow and steroidogenesis.

Author List

Kopf PG, Gauthier KM, Zhang DX, Falck JR, Campbell WB

Authors

William B. Campbell PhD Chair, Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin
David X. Zhang MD, PhD Associate Professor in the Medicine department at Medical College of Wisconsin




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

8,11,14-Eicosatrienoic Acid
Adrenal Glands
Aldosterone
Angiotensin II
Animals
Arachidonic Acid
Arteries
Cattle
Cells, Cultured
Dose-Response Relationship, Drug
Epoxide Hydrolases
In Vitro Techniques
Membrane Potentials
Muscle, Smooth, Vascular
Myocytes, Smooth Muscle
Patch-Clamp Techniques
Potassium Channels
Vasoconstrictor Agents
Vasodilation
Vasodilator Agents
Zona Glomerulosa
jenkins-FCD Prod-482 91ad8a360b6da540234915ea01ff80e38bfdb40a