Saha Manash, Sun Qi-Jian, Hildreth Cara M, Burke Peter G R, Phillips Jacqueline K
Department of Biomedical Sciences, Macquarie University, Sydney, NSW, Australia.
Department of Nephrology, National Institute of Kidney Disease and Urology, Dhaka, Bangladesh.
Front Physiol. 2021 May 25;12:623599. doi: 10.3389/fphys.2021.623599. eCollection 2021.
Carotid body feedback and hypoxia may serve to enhance respiratory-sympathetic nerve coupling (respSNA) and act as a driver of increased blood pressure. Using the Lewis polycystic kidney (LPK) rat model of chronic kidney disease, we examined respSNA in adult female rodents with CKD and their response to acute hypoxia or hypercapnia compared to Lewis control animals. Under urethane anesthesia, phrenic nerve activity, splanchnic sympathetic nerve activity (sSNA), and renal sympathetic nerve activity (rSNA) were recorded under baseline conditions and during mild hypoxic or hypercapnic challenges. At baseline, tonic SNA and blood pressure were greater in female LPK rats versus Lewis rats (all < 0.05) and respSNA was at least two-fold larger [area under the curve (AUC), sSNA: 7.8 ± 1.1 vs. 3.4 ± 0.7 μV s, rSNA: 11.5 ± 3 vs. 4.8 ± 0.7 μV s, LPK vs. Lewis, both < 0.05]. Mild hypoxia produced a larger pressure response in LPK [Δ mean arterial pressure (MAP) 30 ± 6 vs. 12 ± 6 mmHg] and augmented respSNA (ΔAUC, sSNA: 8.9 ± 3.4 vs. 2 ± 0.7 μV s, rSNA: 6.1 ± 1.2 vs. 3.1 ± 0.7 μV s, LPK vs. Lewis, all ≤ 0.05). In contrast, central chemoreceptor stimulation produced comparable changes in blood pressure and respSNA (ΔMAP 13 ± 3 vs. 9 ± 5 mmHg; respSNA ΔAUC, sSNA: 2.5 ± 1 vs. 1.3 ± 0.7 μV s, rSNA: 4.2 ± 0.9 vs. 3.5 ± 1.4 μV s, LPK vs. Lewis, all > 0.05). These results demonstrate that female rats with CKD exhibit heightened respSNA coupling at baseline that is further augmented by mild hypoxia, and not by hypercapnia. This mechanism may be a contributing driver of hypertension in this animal model of CKD.
颈动脉体反馈和低氧可能有助于增强呼吸-交感神经耦合（respSNA），并成为血压升高的驱动因素。利用慢性肾脏病的Lewis多囊肾（LPK）大鼠模型，我们研究了成年雌性CKD啮齿动物的respSNA，以及它们与Lewis对照动物相比对急性低氧或高碳酸血症的反应。在氨基甲酸乙酯麻醉下，在基线条件下以及轻度低氧或高碳酸血症刺激期间记录膈神经活动、内脏交感神经活动（sSNA）和肾交感神经活动（rSNA）。在基线时，雌性LPK大鼠的紧张性SNA和血压高于Lewis大鼠（均P<0.05），且respSNA至少大两倍[曲线下面积（AUC），sSNA：7.8±1.1对3.4±0.7μV·s，rSNA：11.5±3对4.8±0.7μV·s，LPK对Lewis，均P<0.05]。轻度低氧在LPK中产生更大的压力反应[平均动脉压（MAP）变化30±6对12±6 mmHg]并增强了respSNA（AUC变化，sSNA：8.9±3.4对2±0.7μV·s，rSNA：6.1±1.2对3.1±0.7μV·s，LPK对Lewis，均P≤0.05）。相反，中枢化学感受器刺激在血压和respSNA中产生类似的变化（MAP变化13±3对9±5 mmHg；respSNA的AUC变化，sSNA：2.5±1对1.3±0.7μV·s，rSNA：4.2±0.9对3.5±1.4μV·s，LPK对Lewis，均P>0.05）。这些结果表明，患有CKD的雌性大鼠在基线时表现出增强的respSNA耦合，轻度低氧会进一步增强这种耦合，而高碳酸血症则不会。这种机制可能是该CKD动物模型中高血压的一个促成驱动因素。
