Department of Nephrology and Center of Cardiovascular Research, Campus Charité Mitte, Charité-Universitätsmedizin Berlin, Berlin, Germany.
J Urol. 2012 Jul;188(1):316-23. doi: 10.1016/j.juro.2012.02.2552. Epub 2012 May 16.
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.
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.
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.
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.
性别差异和一氧化氮缺乏导致许多慢性肾脏疾病的进展。在单侧输尿管梗阻缓解模型中，我们分析了生物性别和一氧化氮/环鸟苷单磷酸信号刺激对肾脏疾病严重程度和恢复的影响。
雌性和雄性大鼠接受假手术或单侧输尿管梗阻。单侧输尿管梗阻 5 天后，雌性和雄性大鼠被分为梗阻缓解组或梗阻缓解加 7 天可溶性鸟苷酸环化酶刺激剂 BAY 41-8543 治疗组。
与梗阻缓解的雄性大鼠相比，梗阻缓解的雌性大鼠肾脏疾病程度较轻，肾小管间质基质积累和肾小管萎缩明显减少。在每个性别组中，α1 和 β1-可溶性鸟苷酸环化酶的表达均显著增加，但与治疗前相比，雌性大鼠在接受可溶性鸟苷酸环化酶刺激剂治疗后产生的环鸟苷单磷酸明显增多。在每个组中，BAY 41-8543 治疗均显著改善了肾脏基质蛋白扩张、巨噬细胞浸润、肾小管凋亡和萎缩。
女性性别对单侧输尿管梗阻缓解具有保护作用。这与 BAY 41-8543 对可溶性鸟苷酸环化酶和环鸟苷单磷酸产生的敏感性增加有关。在这些雌性和雄性大鼠中，用 BAY 41-8543 增强一氧化氮/环鸟苷单磷酸信号显著加速了梗阻缓解后的肾脏结构恢复，并在很大程度上改善了由于性别差异导致的疾病严重程度的差异。
