Yao Yimin, Hildreth Cara M, Farnham Melissa M, Saha Manash, Sun Qi-Jian, Pilowsky Paul M, Phillips Jacqueline K
aAustralian School of Advanced Medicine, Macquarie University bHeart Research Institute and University of Sydney, Newtown, Sydney, New South Wales, Australia.
J Hypertens. 2015 Jun;33(6):1249-60. doi: 10.1097/HJH.0000000000000535.
The effect of angiotensin II type I receptor (AT1R) inhibition on the pattern of reflex sympathetic nerve activity (SNA) to multiple target organs in the Lewis polycystic kidney (LPK) rat model of chronic kidney disease was determined.
Mean arterial pressure (MAP), splanchnic SNA (sSNA), renal SNA (rSNA) and lumbar SNA (lSNA) were recorded in urethane-anaesthetized LPK and Lewis controls (total n = 39). Baroreflex, peripheral and central chemoreflex, and somatosensory reflex control of SNA (evoked by phenylephrine/sodium nitroprusside infusion, 10% O2 in N2 or 100% N2 ventilation, 5% CO2 ventilation and sciatic nerve stimulation, respectively) were determined before and after administration of losartan (AT1R antagonist 3 mg/kg, intravenous).
Baseline MAP was higher in LPK rats and baroreflex control of sSNA and rSNA, but not lSNA, was reduced. Losartan reduced MAP in both strains and selectively improved baroreflex gain for sSNA (-1.2 ± 0.1 vs. -0.7 ± 0.07 %/mmHg; P < 0.05) in LPK. The peripheral and central chemoreflex increased MAP and all SNA in Lewis controls, but reduced or had no effect on these parameters, respectively, in LPK. The SNA response to somatosensory stimulation was biphasic, with latency to second peak less in LPK. Losartan ameliorated the depressor and sympathoinhibitory responses to peripheral chemoreflex stimulation in the LPK, but did not alter the central chemoreflex or somatosympathetic responses.
Inhibition of the AT1R selectively improved baroreflex control of sSNA and peripheral chemoreflex control of all three sympathetic nerve outflows in the LPK rat, suggesting these anomalies in reflex function are driven in part by angiotensin II.
在慢性肾脏病的Lewis多囊肾（LPK）大鼠模型中，确定了血管紧张素II 1型受体（AT1R）抑制对多个靶器官的反射性交感神经活动（SNA）模式的影响。
在氨基甲酸乙酯麻醉的LPK大鼠和Lewis对照大鼠（总共n = 39）中记录平均动脉压（MAP）、内脏SNA（sSNA）、肾SNA（rSNA）和腰SNA（lSNA）。在给予氯沙坦（AT1R拮抗剂3 mg/kg，静脉注射）之前和之后，分别测定压力反射、外周和中枢化学反射以及SNA的体感反射控制（分别通过注射去氧肾上腺素/硝普钠、在氮气中10%氧气或100%氮气通气、5%二氧化碳通气以及坐骨神经刺激诱发）。
LPK大鼠的基线MAP较高，并且sSNA和rSNA的压力反射控制降低，但lSNA未降低。氯沙坦降低了两种品系的MAP，并选择性地改善了LPK大鼠中sSNA的压力反射增益（-1.2±0.1对-0.7±0.07%/mmHg；P<0.05）。外周和中枢化学反射在Lewis对照大鼠中增加了MAP和所有SNA，但在LPK大鼠中分别降低或对这些参数没有影响。对体感刺激的SNA反应是双相的，LPK大鼠中第二个峰值的潜伏期较短。氯沙坦改善了LPK大鼠对外周化学反射刺激的降压和交感抑制反应，但未改变中枢化学反射或躯体交感反应。
AT1R的抑制选择性地改善了LPK大鼠中sSNA的压力反射控制以及所有三种交感神经输出的外周化学反射控制，表明反射功能中的这些异常部分是由血管紧张素II驱动的。
