title: Interaction between nitric oxide and superoxide in the macula densa in aldosterone-induced alterations of tubuloglomerular feedback.
abstract: Tubuloglomerular feedback (TGF)-mediated constriction of the afferent arteriole is modulated by a balance between release of superoxide (O(2)(-)) and nitric oxide (NO) in macula densa (MD) cells. Aldosterone activates mineralocorticoid receptors that are expressed in the MD and induces both NO and O(2)(-) generation. We hypothesize that aldosterone enhances O(2)(-) production in the MD mediated by protein kinase C (PKC), which buffers the effect of NO in control of TGF response. Studies were performed in microdissected and perfused MD and in a MD cell line, MMDD1 cells. Aldosterone significantly enhanced O(2)(-) generation both in perfused MD and in MMDD1 cells. When aldosterone (10(-7) mol/l) was added in the tubular perfusate, TGF response was reduced from 2.4 ± 0.3 μm to 1.4 ± 0.2 μm in isolated perfused MD. In the presence of tempol, a O(2)(-) scavenger, TGF response was 1.5 ± 0.2 μm. In the presence of both tempol and aldosterone in the tubular perfusate, TGF response was further reduced to 0.4 ± 0.2 μm. To determine if PKC is involved in aldosterone-induced O(2)(-) production, we exposed the O(2)(-) cells to a nonselective PKC inhibitor chelerythrine chloride, a specific PKCα inhibitor Go6976, or a PKCα siRNA, and the aldosterone-induced increase in O(2)(-) production was blocked. These data indicate that aldosterone-stimulated O(2)(-) production in the MD buffers the effect of NO in control of TGF response, an effect that was mediated by PKCα.
authors.affiliation: Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS 39216, USA.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhang
authors.forename: Lin
authors.initials: L
authors.lastname: Lin
authors.forename: Yan
authors.initials: Y
authors.lastname: Lu
authors.forename: Haifeng
authors.initials: H
authors.lastname: Liu
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Duan
authors.forename: Xiaolong
authors.initials: X
authors.lastname: Zhu
authors.forename: Chengwei
authors.initials: C
authors.lastname: Zou
authors.forename: R Davis
authors.initials: RD
authors.lastname: Manning
authors.forename: Ruisheng
authors.initials: R
authors.lastname: Liu
mesh_terms: D000450:Aldosterone / Q000494:pharmacology*; D000818:Animals; D053119:Benzophenanthridines / Q000494:pharmacology; D002227:Carbazoles / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D025461:Feedback, Physiological / Q000187:drug effects*; D007678:Kidney Glomerulus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D007686:Kidney Tubules, Distal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D023421:Models, Animal; D009569:Nitric Oxide / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism; D051571:Protein Kinase C-alpha / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism; D011817:Rabbits; D018161:Receptors, Mineralocorticoid / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism*; D015291:Transforming Growth Factors / Q000378:metabolism
chemical_list: D053119:Benzophenanthridines; D002227:Carbazoles; D004791:Enzyme Inhibitors; D018161:Receptors, Mineralocorticoid; D013481:Superoxides; C081021:Go 6976; D009569:Nitric Oxide; D000450:Aldosterone; D015291:Transforming Growth Factors; C016299:chelerythrine; D051571:Protein Kinase C-alpha; D010100:Oxygen