■先兆子痫是一种严重的妊娠疾病,并发异常的母体血管功能障碍。CNP(C型利钠肽)有助于血管稳态,通过NPR-B(利钠肽受体-B)和NPR-C(利钠肽受体-C)发挥作用。CNP可减轻非妊娠队列中动脉的血管功能障碍;这项研究调查了CNP是否可以在离体先兆子痫模型中扩张母体动脉。
■从剖宫产期间收集的脂肪活检中解剖人网膜动脉。CNP,NPR-B,在妊娠合并先兆子痫(n=6)和血压正常的对照组(n=11)收集的动脉中评估了NPR-CmRNA的表达。使用导线肌电图,我们研究了CNP对血压正常妊娠动脉扩张的影响.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,以模拟与先兆子痫相关的血管收缩。用重组CNP(0.001-100μmol/L)或媒介物处理预收缩的动脉并评估血管舒张。在进一步的研究中,在血清诱导的收缩前,用NPR-B(5µmol/L)和NPR-C(10µmol/L)拮抗剂预孵育动脉(n=4-5),以探索机制信号传导.
■CNP,NPR-B,和NPR-CmRNA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(使用先兆子痫血清)中,CNP有效刺激母体动脉血管舒张。它的血管舒张作用主要是通过激活NPR-B来驱动的;仅对该受体的拮抗作用会抑制CNP的血管舒张。有趣的是,CNP不能减少ET-1驱动的网膜动脉收缩。
■集体,这些数据提示,通过NPR-B增强CNP信号为减少先兆子痫患者全身血管收缩提供了潜在的治疗策略.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: Collectively, these data suggest that enhancing CNP signaling through NPR-B offers a potential therapeutic strategy to reduce systemic vascular constriction in preeclampsia.