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suck abstract from ncbi


10.1097/HJH.0b013e32834786d6

http://scihub22266oqcxt.onion/10.1097/HJH.0b013e32834786d6
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21602712!ä!21602712

suck abstract from ncbi


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pmid21602712      J+Hypertens 2011 ; 29 (7): 1400-10
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  • Dysregulation of renal transient receptor potential melastatin 6/7 but not paracellin-1 in aldosterone-induced hypertension and kidney damage in a model of hereditary hypomagnesemia #MMPMID21602712
  • Yogi A; Callera GE; O'Connor SE; He Y; Correa JW; Tostes RC; Mazur A; Touyz RM
  • J Hypertens 2011[Jul]; 29 (7): 1400-10 PMID21602712show ga
  • RATIONALE: Hyperaldosteronism, important in hypertension, is associated with electrolyte alterations, including hypomagnesemia, through unknown mechanisms. OBJECTIVE: To test whether aldosterone influences renal Mg(2+) transporters, (transient receptor potential melastatin (TRPM) 6, TRPM7, paracellin-1) leading to hypomagnesemia, hypertension and target organ damage and whether in a background of magnesium deficiency, this is exaggerated. METHODS AND RESULTS: Aldosterone effects in mice selectively bred for high-normal (MgH) or low (MgL) intracellular Mg(2+) were studied. Male MgH and MgL mice received aldosterone (350 mug/kg per day, 3 weeks). SBP was elevated in MgL. Aldosterone increased blood pressure and albuminuria and increased urinary Mg(2+) concentration in MgH and MgL, with greater effects in MgL. Activity of renal TRPM6 and TRPM7 was lower in vehicle-treated MgL than MgH. Aldosterone increased activity of TRPM6 in MgH and inhibited activity in MgL. TRPM7 and paracellin-1 were unaffected by aldosterone. Aldosterone-induced albuminuria in MgL was associated with increased renal fibrosis, increased oxidative stress, activation of mitogen-activated protein kinases and nuclear factor-NF-kappaB and podocyte injury. Mg(2+) supplementation (0.75% Mg(2+)) in aldosterone-treated MgL normalized plasma Mg(2+), increased TRPM6 activity and ameliorated hypertension and renal injury. Hence, in a model of inherited hypomagnesemia, TRPM6 and TRPM7, but not paracellin-1, are downregulated. Aldosterone further decreased TRPM6 activity in hypomagnesemic mice, a phenomenon associated with hypertension and kidney damage. Such effects were prevented by Mg(2+) supplementation. CONCLUSION: Amplified target organ damage in aldosterone-induced hypertension in hypomagnesemic conditions is associated with dysfunctional Mg(2+)-sensitive renal TRPM6 channels. Novel mechanisms for renal effects of aldosterone and insights into putative beneficial actions of Mg(2+), particularly in hyperaldosteronism, are identified.
  • |*Disease Models, Animal[MESH]
  • |Aldosterone/*toxicity[MESH]
  • |Animals[MESH]
  • |Claudins[MESH]
  • |Hypercalciuria/*physiopathology[MESH]
  • |Hypertension/chemically induced/*physiopathology[MESH]
  • |Membrane Proteins/*physiology[MESH]
  • |Mice[MESH]
  • |Nephrocalcinosis/*physiopathology[MESH]
  • |Oxidative Stress[MESH]
  • |Renal Tubular Transport, Inborn Errors/*physiopathology[MESH]


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