ArticleAmerican journal of physiology. Renal physiology2011
Aldosterone stimulates superoxide production in macula densa cells.
Article in American journal of physiology. Renal physiology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 35 citations in OpenAlex.
- Chronic Stress and the Brain-Kidney Axis in Renal Injury: From Neuroendocrine Dysregulation to Kidney Damage.International journal of molecular sciences · 2026Review
- What can urinary exosomes tell us?Cellular and molecular life sciences : CMLS · 2021Review
- Serum Alpha-1-Acid Glycoprotein-1 and Urinary Extracellular Vesicle miR-21-5p as Potential Biomarkers of Primary Aldosteronism.Frontiers in immunology · 2021Article
- Urinary Exosomes and Their Cargo: Potential Biomarkers for Mineralocorticoid Arterial Hypertension?Frontiers in endocrinology · 2017Review
- Rapid Action of Aldosterone on Protein Levels of Sodium-Hydrogen Exchangers and Protein Kinase C Beta Isoforms in Rat Kidney.International journal of endocrinology · 2017Article
- Mechanisms of connecting tubule glomerular feedback enhancement by aldosterone.American journal of physiology. Renal physiology · 2016Article
- Third-generation Mineralocorticoid Receptor Antagonists: Why Do We Need a Fourth?Journal of cardiovascular pharmacology · 2016Review
- Angiotensin and mineralocorticoid receptor antagonism attenuates cardiac oxidative stress in angiotensin II-infused rats.Clinical and experimental pharmacology & physiology · 2015Article
- Shear stress blunts tubuloglomerular feedback partially mediated by primary cilia and nitric oxide at the macula densa.American journal of physiology. Regulatory, integrative and comparative physiology · 2015Article
- Review
- The multifaceted mineralocorticoid receptor.Comprehensive Physiology · 2014Review
- Expression of mineralocorticoid and glucocorticoid receptors in preautonomic neurons of the rat paraventricular nucleus.American journal of physiology. Regulatory, integrative and comparative physiology · 2014Article
- Enhanced expression and activity of Nox2 and Nox4 in the macula densa in ANG II-induced hypertensive mice.American journal of physiology. Renal physiology · 2014Article
- Aldosterone signaling through transient receptor potential melastatin 7 cation channel (TRPM7) and its α-kinase domain.Cellular signalling · 2013Article
- Testosterone enhances tubuloglomerular feedback by increasing superoxide production in the macula densa.American journal of physiology. Regulatory, integrative and comparative physiology · 2013Article
- Interaction between nitric oxide and superoxide in the macula densa in aldosterone-induced alterations of tubuloglomerular feedback.American journal of physiology. Renal physiology · 2013Article
- Aldosterone blunts tubuloglomerular feedback by activating macula densa mineralocorticoid receptors.Hypertension (Dallas, Tex. : 1979) · 2012Article
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Two major factors which regulate tubuloglomerular feedback (TGF)-mediated constriction of the afferent arteriole are release of superoxide (O(2)(-)) and nitric oxide (NO) by macula densa (MD) cells. MD O(2)(-) inactivates NO; however, among the factors that increase MD O(2)(-) release, the role of aldosterone is unclear. We hypothesize that aldosterone activates the mineralocorticoid receptor (MR) on MD cells, resulting in increased O(2)(-) production due to upregulation of cyclooxygenase-1 (COX-2) and NOX-2, and NOX-4, isoforms of NAD(P)H oxidase. Studies were performed on MMDD1 cells, a renal epithelial cell line with properties of MD cells. RT-PCR and Western blotting confirmed the expression of MR. Aldosterone (10(-8) mol/l for 30 min) doubled MMDD1 cell O(2)(-) production, and this was completely blocked by MR inhibition with 10(-5) mol/l eplerenone. RT-PCR, real-time PCR, and Western blotting demonstrated aldosterone-induced increases in COX-2, NOX-2, and NOX-4 expression. Inhibition of COX-2 (NS398), NADPH oxidase (apocynin), or a combination blocked aldosterone-induced O(2)(-) production to the same degree. These data suggest that aldosterone-stimulated MD O(2)(-) production is mediated by COX-2 and NADPH oxidase. Next, COX-2 small-interfering RNA (siRNA) specifically decreased COX-2 mRNA without affecting NOX-2 or NOX-4 mRNAs. In the presence of the COX-2 siRNA, the aldosterone-induced increases in COX-2, NOX-2, and NOX-4 mRNAs and O(2)(-) production were completely blocked, suggesting that COX-2 causes increased expression of NOX-2 and NOX-4. In conclusion 1) MD cells express MR; 2) aldosterone increases O(2)(-) production by activating MR; and 3) aldosterone stimulates COX-2, which further activates NOX-2 and NOX-4 and generates O(2)(-). The resulting balance between O(2)(-) and NO in the MD is important in modulating TGF.
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