title: Impact of biological gender and soluble guanylate cyclase stimulation on renal recovery after relief of unilateral ureteral obstruction.
abstract: OBJECTIVE
  Gender difference and nitric oxide deficiency contribute to the progression of many chronic kidney diseases. In a model of unilateral ureteral obstruction relief we analyzed the impact of biological gender and nitric oxide/cyclic guanosine monophosphate signaling stimulation on renal disease severity and restoration.
  
  
  METHODS
  Female and male rats underwent sham surgery or unilateral ureteral obstruction. After 5-day unilateral ureteral obstruction female and male rats were assigned to obstruction relief alone or obstruction relief plus 7-day treatment with the soluble guanylate cyclase stimulator BAY 41-8543.
  
  
  RESULTS
  Compared to male rats with obstruction relief renal disease was less severe in female rats, which had significantly less tubulointerstitial matrix accumulation and tubular atrophy. In each gender group α1 and β1-soluble guanylate cyclase was comparably and significantly increased but female rats produced significantly more cyclic guanosine monophosphate after treatment with the soluble guanylate cyclase stimulator. In each group BAY 41-8543 treatment was associated with significant amelioration of renal matrix protein expansion, macrophage infiltration, tubular apoptosis and atrophy.
  
  
  CONCLUSIONS
  Female gender is protective for unilateral ureteral obstruction relief. This was linked to higher sensitivity of the soluble guanylate cyclase enzyme and cyclic guanosine monophosphate production in response to BAY 41-8543. In these female and male rats enhancing the signaling of nitric oxide/cyclic guanosine monophosphate with BAY 41-8543 significantly accelerated the restoration of renal architecture after obstruction relief and largely ameliorated the differences in disease severity due to the gender disparity.
authors.affiliation: Department of Nephrology and Center of Cardiovascular Research, Campus Charité Mitte, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Yingrui
authors.initials: Y
authors.lastname: Wang-Rosenke
authors.forename: Alice
authors.initials: A
authors.lastname: Mika
authors.forename: Dymtro
authors.initials: D
authors.lastname: Khadzhynov
authors.forename: Tanja
authors.initials: T
authors.lastname: Loof
authors.forename: Hans-Hellmut
authors.initials: HH
authors.lastname: Neumayer
authors.forename: Harm
authors.initials: H
authors.lastname: Peters
mesh_terms: D000284:Administration, Oral; D000818:Animals; D017209:Apoptosis; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005786:Gene Expression Regulation; D006162:Guanylate Cyclase / Q000096:biosynthesis / Q000235:genetics*; D020287:In Situ Nick-End Labeling; D007668:Kidney / Q000502:physiology*; D008297:Male; D009025:Morpholines / Q000008:administration & dosage / Q000627:therapeutic use*; D011743:Pyrimidines / Q000008:administration & dosage / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists / Q000096:biosynthesis / Q000235:genetics*; D020127:Recovery of Function; D012720:Severity of Illness Index; D012737:Sex Factors; D000071756:Soluble Guanylyl Cyclase; D016896:Treatment Outcome; D014517:Ureteral Obstruction / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology
chemical_list: C450679:BAY 41-8543; D009025:Morpholines; D011743:Pyrimidines; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D006162:Guanylate Cyclase; D000071756:Soluble Guanylyl Cyclase