In sleep apnea, airway obstruction causes intermittent hypoxia (IH). In animal studies, IH-dependent hypertension is associated with loss of vasodilator hydrogen sulfide (H₂S), and increased H₂S activation of sympathetic nervous system (SNS) activity in the carotid body. We previously reported that inhibiting cystathionine γ-lyase (CSE) to prevent H₂S synthesis augments vascular resistance in control rats. The goal of this study was to evaluate the contribution of IH-induced changes in CSE signaling to increased blood pressure and vascular resistance. We hypothesized that chronic IH exposure eliminates CSE regulation of blood pressure (BP) and vascular resistance. In rats instrumented with venous catheters, arterial telemeters, and flow probes on the main mesenteric artery, the CSE inhibitor DL-propargylglycine (PAG, 50 mg/kg/day i.v. for 5 days) increased BP in Sham rats but decreased BP in IH rats (in mmHg, Sham (n = 11): 114±4 to 131±6; IH (n = 8): 131±8 to 115±7 mmHg, p<0.05). PAG treatment increased mesenteric vascular resistance in Sham rats but decreased it in IH rats (Day 5/Day 1: Sham: 1.50 ± 0.07; IH: 0.85 ± 0.19, p<0.05). Administration of the ganglionic blocker hexamethonium (to evaluate SNS activity) decreased mesenteric resistance in PAG-treated Sham rats more than in saline-treated Sham rats or PAG-treated IH rats. CSE immunoreactivity in IH carotid bodies compared to those from Sham rats. However, CSE staining in small mesenteric arteries was less in arteries from IH compared to Sham rats but not different in larger arteries (inner diameter > 200 mm). These results suggest endogenous H₂S regulates blood pressure and vascular resistance but this control is lost after IH exposure with decreased CSE expression in resistance size arteries. IH exposure concurrently increases carotid body CSE expression and relative SNS control of blood pressure suggesting both vascular and carotid body H₂S generation contribute to blood pressure regulation.

中文翻译：

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模拟睡眠呼吸暂停会改变硫化氢对血流和压力的调节

在睡眠呼吸暂停中，气道阻塞会导致间歇性缺氧 (IH)。在动物研究中，IH 依赖性高血压与血管扩张剂硫化氢 (H ₂ S)的损失以及颈动脉体中交感神经系统 (SNS) 活性的H _{2 S 激活增加有关。}我们之前报道过抑制胱硫醚γ-裂合酶 (CSE) 以防止 H ₂S 合成增加了对照大鼠的血管阻力。本研究的目的是评估 IH 诱导的 CSE 信号变化对血压和血管阻力增加的贡献。我们假设慢性 IH 暴露消除了 CSE 对血压 (BP) 和血管阻力的调节。在使用静脉导管、动脉遥测仪和在肠系膜主动脉上的流量探头的大鼠中，CSE 抑制剂 DL-炔丙基甘氨酸（PAG，50 mg/kg/天，静脉注射 5 天）增加了 Sham 大鼠的血压，但降低了 IH 大鼠的血压（以 mmHg 为单位，Sham（n = 11）：114±4 至 131±6；IH（n = 8）：131±8 至 115±7 mmHg，p<0.05）。PAG 治疗增加了 Sham 大鼠的肠系膜血管阻力，但降低了 IH 大鼠的肠系膜血管阻力（第 5 天/第 1 天：Sham：1.50 ± 0.07；IH：0.85 ± 0.19，p<0.05）。与生理盐水处理的 Sham 大鼠或 PAG 处理的 IH 大鼠相比，给予神经节阻滞剂六甲铵（以评估 SNS 活性）更能降低 PAG 处理的 Sham 大鼠的肠系膜阻力。与 Sham 大鼠相比，IH 颈动脉体中的 CSE 免疫反应性。然而，与 Sham 大鼠相比，来自 IH 的动脉中小肠系膜动脉的 CSE 染色较少，但在较大的动脉（内径 > 200 mm）中没有差异。这些结果表明内源性 H 与 Sham 大鼠相比，来自 IH 的动脉中小肠系膜动脉的 CSE 染色较少，但在较大的动脉（内径 > 200 mm）中没有差异。这些结果表明内源性 H 与 Sham 大鼠相比，来自 IH 的动脉中小肠系膜动脉的 CSE 染色较少，但在较大的动脉（内径 > 200 mm）中没有差异。这些结果表明内源性 H₂ S 调节血压和血管阻力，但这种控制在 IH 暴露后失去，阻力大小的动脉中 CSE 表达降低。IH 暴露同时增加颈动脉体 CSE 表达和相对 SNS 对血压的控制，表明血管和颈动脉体 H ₂ S 的产生有助于血压调节。