PURPOSE: 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. MATERIALS AND 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.
PURPOSE: 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. MATERIALS AND 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: Ana I Casas; V Thao-Vi Dao; Andreas Daiber; Ghassan J Maghzal; Fabio Di Lisa; Nina Kaludercic; Sonia Leach; Antonio Cuadrado; Vincent Jaquet; Tamara Seredenina; Karl H Krause; Manuela G López; Roland Stocker; Pietro Ghezzi; Harald H H W Schmidt Journal: Antioxid Redox Signal Date: 2015-11-10 Impact factor: 8.401
Authors: Elisabeth Schinner; Veronika Wetzl; Andrea Schramm; Frieder Kees; Peter Sandner; Johannes-Peter Stasch; Franz Hofmann; Jens Schlossmann Journal: FEBS Open Bio Date: 2017-03-01 Impact factor: 2.693