title: Ouabain chronic infusion enhances the growth and steroidogenic capacity of rat adrenal zona glomerulosa: the possible involvement of the endothelin system.
abstract: Ouabain, an inhibitor of the Na+/K+-ATPase, has been reported to affect the secretory activity of the adrenal cortex, and especially of zona glomerulosa (ZG). However, conflicting results were obtained, depending on the experimental condition used since ouabain appears to interact with angiotensin-II (Ang-II) and its action to be influenced by the electrolyte balance. Hence, we investigated the effects of prolonged (4-month) infusion with ouabain on the rat adrenal cortex. Ouabain raised the plasma concentrations of aldosterone, corticosterone and endothelin-1 (ET-1), without affecting either systolic blood pressure (SBP) or plasma renin activity (PRA). The treatment caused a marked hypertrophy of ZG and ZG cells, which mainly ensued from increases in the volume of the mitochondrial and smooth-endoplasmic-reticulum compartments, where the enzymes of steroid synthesis are located. Conversely, the volume of the lipid-droplet compartment, which stores cholesterol utilized in steroid-hormone production, underwent a striking decrease. Zona fasciculata and its parenchymal cells were not affected. Basal and maximally agonist (ACTH, Ang-II and ET-1)-stimulated in vitro mineralocorticoid secretion from adrenal slices was also notably enhanced by ouabain administration. Collectively, these findings indicate that prolonged treatment with ouabain selectively stimulates the growth and steroidogenic capacity of the rat adrenal ZG. The possibility that the activation of the renin-angiotensin system may be involved in this effect of ouabain is ruled out by the lack of significant changes in SBP and PRA. Instead, our results suggest the possible involvement of ET-1, the plasma level of which is elevated in ouabain-infused rats.
authors.affiliation: Department of Human Anatomy and Physiology, Section of Anatomy, School of Medicine, University of Padua, I-35121 Padua, Italy.
authors.forename: Giuliano
authors.initials: G
authors.lastname: Neri
authors.forename: Renzo
authors.initials: R
authors.lastname: De Toni
authors.forename: Cinzia
authors.initials: C
authors.lastname: Tortorella
authors.forename: Piera
authors.initials: P
authors.lastname: Rebuffat
authors.forename: Sergio
authors.initials: S
authors.lastname: Bova
authors.forename: Gabriella
authors.initials: G
authors.lastname: Cargnelli
authors.forename: Lucia
authors.initials: L
authors.lastname: Petrelli
authors.forename: Raffaella
authors.initials: R
authors.lastname: Spinazzi
authors.forename: Gastone G
authors.initials: GG
authors.lastname: Nussdorfer
mesh_terms: D000450:Aldosterone / Q000097:blood; D000818:Animals; D001794:Blood Pressure; D003345:Corticosterone / Q000097:blood; D019332:Endothelin-1 / Q000097:blood*; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D008297:Male; D010042:Ouabain / Q000008:administration & dosage / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D011921:Rats, Inbred WKY; D012083:Renin / Q000378:metabolism; D015384:Zona Glomerulosa / Q000033:anatomy & histology / Q000187:drug effects* / Q000502:physiology*
chemical_list: D019332:Endothelin-1; D004791:Enzyme Inhibitors; D000450:Aldosterone; D010042:Ouabain; D012083:Renin; D003345:Corticosterone