title: Angiotensin II regulates adrenal vascular tone through zona glomerulosa cell-derived EETs and DHETs.
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.
authors.affiliation: Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
authors.forename: Phillip G
authors.initials: PG
authors.lastname: Kopf
authors.forename: Kathryn M
authors.initials: KM
authors.lastname: Gauthier
authors.forename: David X
authors.initials: DX
authors.lastname: Zhang
authors.forename: John R
authors.initials: JR
authors.lastname: Falck
authors.forename: William B
authors.initials: WB
authors.lastname: Campbell
mesh_terms: D015126:8,11,14-Eicosatrienoic Acid / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D000311:Adrenal Glands / Q000098:blood supply; D000450:Aldosterone / Q000378:metabolism; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D001158:Arteries / Q000187:drug effects* / Q000502:physiology; D002417:Cattle; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004851:Epoxide Hydrolases / Q000378:metabolism; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000378:metabolism / Q000494:pharmacology; D015384:Zona Glomerulosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
chemical_list: C107016:14,15-dihydroxyeicosatrienoic acid; D015221:Potassium Channels; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D000804:Angiotensin II; D016718:Arachidonic Acid; D000450:Aldosterone; C046782:14,15-epoxy-5,8,11-eicosatrienoic acid; D004851:Epoxide Hydrolases; D015126:8,11,14-Eicosatrienoic Acid