BACKGROUND Preeclampsia is a serious condition of pregnancy, complicated by aberrant maternal vascular dysfunction. CNP (C-type natriuretic peptide) contributes to vascular homeostasis, acting through NPR-B (natriuretic peptide receptor-B) and NPR-C (natriuretic peptide receptor-C). CNP mitigates vascular dysfunction of arteries in nonpregnant cohorts; this study investigates whether CNP can dilate maternal arteries in ex vivo preeclampsia models. METHODS Human omental arteries were dissected from fat biopsies collected during cesarean section. CNP, NPR-B, and NPR-C mRNA expression was assessed in arteries collected from pregnancies complicated by preeclampsia (n=6) and normotensive controls (n=11). Using wire myography, we investigated the effects of CNP on dilation of arteries from normotensive pregnancies. Arteries were preconstricted with either serum from patients with preeclampsia (n=6) or recombinant ET-1 (endothelin-1; vasoconstrictor elevated in preeclampsia; n=6) to model vasoconstriction associated with preeclampsia. Preconstricted arteries were treated with recombinant CNP (0.001-100 µmol/L) or vehicle and vascular relaxation assessed. In further studies, arteries were preincubated with NPR-B (5 µmol/L) and NPR-C (10 µmol/L) antagonists before serum-induced constriction (n=4-5) to explore mechanistic signaling. RESULTS CNP, NPR-B, and NPR-C mRNAs were not differentially expressed in omental arteries from preeclamptic pregnancies. CNP potently stimulated maternal artery vasorelaxation in our model of preeclampsia (using preeclamptic serum). Its vasodilatory actions were driven through the activation of NPR-B predominantly; antagonism of this receptor alone dampened CNP vasorelaxation. Interestingly, CNP did not reduce ET-1-driven omental artery constriction. CONCLUSIONS Collectively, these data suggest that enhancing CNP signaling through NPR-B offers a potential therapeutic strategy to reduce systemic vascular constriction in preeclampsia.

中文翻译：

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探索 C 型钠尿肽治疗先兆子痫的潜力。


背景先兆子痫是一种严重的妊娠病症，由异常的母体血管功能障碍并发。 CNP（C 型利钠肽）通过 NPR-B（利钠肽受体-B）和 NPR-C（利钠肽受体-C）发挥作用，有助于血管稳态。 CNP 可减轻非妊娠人群的动脉血管功能障碍；本研究探讨 CNP 是否可以在离体先兆子痫模型中扩张母体动脉。方法 从剖腹产期间收集的脂肪活检中解剖出人网膜动脉。在患有先兆子痫 (n = 6) 和血压正常对照 (n = 11) 的妊娠中收集的动脉中评估了 CNP、NPR-B 和 NPR-C mRNA 表达。使用钢丝肌动描记法，我们研究了 CNP 对血压正常妊娠时动脉扩张的影响。用来自先兆子痫患者的血清 (n=6) 或重组 ET-1（内皮素-1；先兆子痫中血管收缩剂升高；n=6）对动脉进行预收缩，以建立与先兆子痫相关的血管收缩模型。用重组 CNP (0.001-100 µmol/L) 或载体处理预收缩动脉并评估血管松弛。在进一步的研究中，在血清诱导收缩之前将动脉与 NPR-B (5 µmol/L) 和 NPR-C (10 µmol/L) 拮抗剂一起预孵育 (n=4-5)，以探索信号传导机制。结果 CNP、NPR-B 和 NPR-C mRNA 在先兆子痫妊娠的网膜动脉中没有差异表达。在我们的先兆子痫模型中（使用先兆子痫血清），CNP 有效刺激母动脉血管舒张。其血管舒张作用主要是通过 NPR-B 的激活来驱动的；该受体单独的拮抗作用可抑制 CNP 血管舒张作用。有趣的是，CNP 并没有减少 ET-1 驱动的网膜动脉收缩。 结论 总的来说，这些数据表明通过 NPR-B 增强 CNP 信号传导为减少先兆子痫的全身血管收缩提供了潜在的治疗策略。