Steroid-producing cells regulate arterial tone of adrenal cortical arteries.
Adrenal blood flow is coupled to adrenal hormone secretion. ACTH increases adrenal blood flow and stimulates the secretion of aldosterone and cortisol in vivo. However, ACTH does not alter vascular tone of isolated adrenal cortical arteries. Mechanisms underlying this discrepancy remain unsolved. The present study examined the effect of zona glomerulosa (ZG) cells on cortical arterial tone. ZG cells (10(5) to 10(7) cells) and ZG cell-conditioned medium relaxed preconstricted adrenal arteries (maximal relaxations = 79 +/- 4 and 66 +/- 4%, respectively). In adrenal arteries coincubated with a small number of ZG cells (0.5-1 x 10(6)), ACTH (10(-12) to 10(-8) m) induced concentration-dependent relaxations (maximal relaxation = 67 +/- 4%). Similarly, ACTH (10(-8) m) dilated (55 +/- 10%) perfused arteries embedded in adrenal cortical slices. ZG cell-dependent relaxations to ACTH were endothelium-independent and inhibited by high extracellular K(+) (60 mm); the K(+) channel blocker, iberiotoxin (100 nm); the cytochrome P450 inhibitors SKF 525A (10 microm) and miconazole (10 microm); and the epoxyeicosatrienoic acid (EET) antagonist 14,15-EEZE (2 microm). Four EET regioisomers were identified in ZG cell-conditioned media. EET production was stimulated by ACTH. We conclude that ZG cells release EETs and this release is stimulated by ACTH. Interaction of endocrine and vascular cells represents a mechanism for regulating adrenal blood flow and couples steroidogenesis to increased blood flow.
Zhang
David X
DX
Department of Pharmacology and Toxicology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, Wisconsin 53226, USA.
Gauthier
Kathryn M
KM
Falck
John R
JR
Siddam
Anjaiah
A
Campbell
William B
WB
D000305:Adrenal Cortex Hormones / Q000096:biosynthesis / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D001158:Arteries / Q000502:physiology*; D002417:Cattle; D017077:Culture Media, Conditioned / Q000494:pharmacology; D045462:Endothelium-Dependent Relaxing Factors / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D025461:Feedback, Physiological / Q000502:physiology; D006728:Hormones / Q000494:pharmacology; D009924:Organ Culture Techniques; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D015384:Zona Glomerulosa / Q000098:blood supply / Q000166:cytology / Q000502:physiology
D000305:Adrenal Cortex Hormones; D017077:Culture Media, Conditioned; D045462:Endothelium-Dependent Relaxing Factors; D004791:Enzyme Inhibitors; D006728:Hormones; D016718:Arachidonic Acid; D000324:Adrenocorticotropic Hormone