刺激家兔肾内感受器和肾传入神经的血流动力学效应

在39只麻醉家兔观察刺激肾脏机械和化学感受器以及电刺激肾传入神经的血流动力学效应。增加输尿管压8—22mmHg 及经输尿管向肾盂内逆向灌注 NaCl(1.0 mol/L)及 KCl(0.15mol/L)溶液时,引起平均动脉压(MAP)和心率(HR)下降;切断双侧缓冲神经后,MAP 降低更为显著。电刺激肾传入神经时,HR 减慢,MAP、肠系膜动脉和后肢动脉灌流压降低,左心室收缩压及其微分值下降,心输出量(CO)和总外周阻力(TPR)减小;切断双侧窦神经和减压神经后,除 HK、CO 和 TPR 外,其余各血流动力学指标的减弱更为显著。由此提示,动脉压力感受器反射对肾传入神经激活的心血管效应有缓冲作用。     

腺苷对家兔颈动脉体化学感受器活动的影响

在39只乌拉坦麻醉家兔,记录了腺苷作用于颈动脉体时窦神经化学感受性传入单位的放电活动。全部实验中共记录了73个有自发放电的化学感受性单位。所得结果如下:(1)颈动脉内注射腺苷(10ug/kg)时,在55个单位中有51个的放电频率由0.76±0.10增加到1.53±0.23 imp/s(P<0.001),部分实验中有新的单位被激活。(2)在隔离的颈动脉窦灌流液中加入腺苷(0.5,1.0、5.0、10、50和100μg/kg)时,9个单位的放电频率由0.51±0.06分别增加到0.58±0.07、0.78±0.13、0.96±0.15、1.11±0.017、1.34±0.21和1.38±0.18imp/s,有明显的剂量依赖性(P<0.001).(3)9个自发放电频率为1.30±0.40 imp/s 的单位,在颈动脉内注射多巴胺(50μg/kg)后,其放电频率减慢至0.56±0.19imp/s(P<0.001)。在多巴胺作用的基础上再注射腺苷。可使放电频率增加到1.07±0.28imp/s,但与注射多巴胺前的腺苷效应相比,此增值明显减小(P<0.001)。根据以上结果,我们推测腺苷对颈动脉体化学感受器的兴奋作用,可能与其作用于感受器复合体的突触前膜,从而使颈动脉体内抑制性递质多巴胺释放减少,以及腺苷直接兴奋化学感受性神经末梢有关。     

心房钠尿因子对颈动脉窦压力感受器反射的易化作用

在麻醉大鼠观察了心房肽Ⅲ(AtriopeptinⅡ,APⅡ)对颈动脉窦压力感受器活动的影响,并在麻醉家兔观察了APⅡ作用于颈动脉窦区时窦神经传入放电的改变。结果如下:(1)用APⅡ(1μg/ml)隔离灌流大鼠左侧颈动脉窦区(n=10),压力感受器反射的阈压(TP)无明显改变,平衡压(EP)由101±2.8降至95±2.0 mmHg(P<0.05),饱和压(SP)由202±5.2降至168±6.1 mmHg(P<0.001),而工作范围(OR)由128±5.5减至93±6.3mmHg(P<0.001),压力感受器机能曲线向左下方移位,曲线最大斜率(PS)由0.77±0.04增大为1.07±0.13mmHg·mmHg~(-1)(P<0.05);(2)在用硝普钠(NP,0.5μg/ml)灌流的动物(n=6),TP和 EP 无改变,SP 由188±6.4升至218±6.0 mmHg(P<0.01),OR 由107±6.9增至132±7.6 mmHg(P<0.05),硝普钠对压力感受器机能曲线及其 PS 无显著影响;(3)恒压隔离灌流兔颈动脉窦区时,窦神经传入放电具有良好的稳定性,升高窦内压(ISP)时,窦神经传入放电也随之增多。用 APⅡ(1μg/ml)恒压灌流时,窦神经传入放电增加20.9±3.9%(n=6,P<0.01),冲洗掉 APⅡ后,窦神经传入放电恢复至对照水平。以上结果显示,APⅢ可使大鼠颈动脉窦压力感受器机能曲线向左下方移位,曲线最大斜率增大以及兔窦神经传入放电增加,表明 APⅡ对颈动脉窦压力感受器活动有易化作用。这     

肾动脉内注射L-精氨酸抑制肾神经传入纤维的自发活动

研究旨在应用记录肾传人神经多单位和单位放电的方法,观察肾动脉内注射L—精氨酸对麻醉家兔肾神经传人纤维自发放电活动的影响。结果表明：(1）肾动脉内注射L—精氨酸(0．05、0．24和0．48mmol/kg)可呈剂量依赖性地抑制肾传人纤维的活动,而动脉血压不变;(2)静脉内预先注射一氧化氮合酶抑制剂L—NAME(0．11mmol/kg),可完全阻断L—精氨酸对肾传人纤维的抑制;(3)肾动脉注射一氧化氮(N0)供体SIN—1(3．75μmol/kg)也可抑制肾传入神经的活动。以上结果提示：肾动脉内应用N0前体L—精氨酸和N0供体SIN—1均可抑制肾传入纤维的自发活动。     

肾动脉内注射辣椒素兴奋肾神经传入纤维的自发活动

应用记录肾传入神经多单位和单位放电的方法,观察肾动脉内注射辣椒素对麻醉家兔肾神经传入纤维自发放电活动的影响。结果表明：(1)肾动脉内注射辣椒素20、40和60nmol／kg可呈剂量依赖性地兴奋肾传入纤维的活动,而动脉血压不变;(2)静脉内预先应用辣椒素受体阻断剂钌红(40mmol／kg),可完全阻断辣椒素对肾传人纤维的兴奋作用。(3)静脉内预先注射一氧化氮合酶抑制剂L-NAME(0．1mmol／kg),能延长并增强肾传入神经对辣椒素的反应。以上结果提示：肾动脉内应用辣椒素可兴奋肾传人纤维的自发放电活动。一氧化氮作为抑制因素参与辣椒素诱导的肾传入神经兴奋。     

植物雌激素三羟异黄酮抑制麻醉大鼠颈动脉窦压力感受器反射

采用隔离灌流麻醉雄性大鼠颈动脉窦技术,观察了植物雌激素三羟异黄酮（genistein,GST）对颈动脉窦压力感受器反射的影响。其结果如下:（1）以GST（50μmol/L）隔离灌流颈动脉窦区时,压力感受器机能曲线向右上方移位,曲线最大斜率（peak slope,PS）由0.36±0.01降至0.23±0.01（P<0.001）;反射性血压下降幅度（reflex decrease,RD）由39.75±1.58降至27.00±0.60 mmHg（P<0.001）,阈压（TP）和饱和压（SP）分别从65.63±2.10和192.23±3.90升至82.05±1.95mmHg（P<0.001）和215.76±3.75mmHg（P<0.001）。其中RD、PS和TP呈明显的剂量依赖性;（2）用Ca2+通道激动剂Bay K 8644（500 nmol/L）预处理后,能取消GST（50 μmol/L）对压力感受器反射的抑制作用;（3）预先灌流NO合酶阻断剂（L-NAME,100μmol/L）,不能阻断GST（50μmol/L）对压力感受器反射的抑制效应。以上结果提示,GST可能通过阻断Ca2+通道途径而抑制大鼠颈动脉窦压力感受器反射,并非由血管内皮细胞释放NO所致。     

颈动脉注射肾上腺髓质素对去缓冲神经大鼠最后区神经元自发放电的影响

在63只切断两侧缓冲神经的麻醉sprague-Dawley大鼠,应用细胞外记录的电生理学方法,观察颈内动脉注射肾上腺髓质素(adrenomedullin,AM)对最后区(area postrema,AP)神经元自发电活动的影响。实验结果如下:(1)在记录到的78个自发放电单位中,颈内动脉内注射AM(0.3 nmol/kg),引起其中47个单位的自发放电频率由2.99±0.24增加到4.79±0.29 spikes/s(P<0.001),20个单位自发放电频率由3.24±0.46下降至1.97±0.37 spikes/s(P<0.001),另外11个单位自发放电频率无明显改变;平均动脉压和心率无明显变化。(2)颈内动脉注射降钙素基因相关肽受体阻断剂CGRP_(8-37)(3 nmol/kg)不能改变AM对自发放电的兴奋效应;(3)颈内动脉注射L-精氨酸(30 mg/kg)可减弱AM对自发放电的兴奋效应。以上结果提示,AM对最后区神经元有兴奋作用,此作用不是由降钙素基因相关肽受体介导,但可被NO前体L-精氨酸所减弱。     

皮层抑制对大鼠丘脑底核自发放电的影响

目的:观察皮层抑制对正常及帕金森病(PD)大鼠丘脑底核(STN)神经元自发放电的影响。方法:采用玻璃微电极细胞外记录法,观察正常和PD大鼠STN神经元的放电活动及脑内微量注射KCl后,两组大鼠STN神经元放电频率的变化。结果:对照组和PD组大鼠STN神经元放电频率分别为(9.78±0.71)Hz和(23.81±1.08)Hz,PD组大鼠放电频率显著高于对照组(P<0.01),且呈爆发式放电的神经元比例明显高于对照组(P<0.05)。皮层注射KCl后,经过较长的潜伏期,两组大鼠STN神经元放电频率均明显降低,后缓慢恢复。结论:PD大鼠STN神经元放电频率增高,爆发式放电增多,而抑制皮层可使这种异常放电得到改善,提示皮层兴奋性的改变可能是PD中STN活动增强的另一个诱因。     

肾神经在肾缺血预处理对麻醉家兔心脏保护中的作用

在氨基甲酸乙酯麻醉家兔上,观察肾脏缺血预处理(RIP)对缺血-再灌注心肌的影响,旨在证实RIP对心肌有无保护效应,并明确肾神经在其中的作用。所得结果如下(1)在心脏45min缺血和180min再灌注过程中,血压、心率和心肌耗氧量呈进行性下降;心外膜电图ST段在缺血期明显抬高,再灌注过程中逐渐恢复到基础对照值。心肌梗塞范围占缺血心肌的55.80±1.25%。(2)RIP时心肌梗塞范围为36.51±2.8%,较单纯心肌缺血-再灌注显著减少(P<0.01),表明RIP对心肌有保护作用。(3)肾神经切断可取消RIP对心肌的保护效应,但肾神经切断本身对单纯缺血-再灌注所致的心肌梗死范围无明显影响。(4)肾缺血(10min)时,肾传入神经放电活动由0.14±0.08增至0.65±0.12imp/s(P<0.01)。(5)预先应用腺苷受体拮抗剂8-苯茶碱可明显减弱肾缺血所激活的肾传入神经活动,提示肾传入活动的增强是由肾缺血产生的腺苷所介导。以上结果表明,肾短暂缺血-再灌注所诱发的肾神经传入活动在RIP心肌保护效应中起重要作用。     

K_(ATP)通道开放剂对颈动脉窦压力感受器反射的易化作用

在 30只隔离灌流颈动脉窦区的麻醉大鼠 ,观察了KATP通道开放剂 (cromakalim ,Cro)对颈动脉窦压力感受器反射的影响。结果如下 :( 1)以Cro ( 10 μmol/L)隔离灌流大鼠左侧颈动脉窦区时 ,压力感受器机能曲线向左下方移位 ,曲线最大斜率 (PS)由 0 36± 0 0 1增至 0 48± 0 0 1kPa/kPa (P <0 0 0 1) ,反射性血压下降幅度 (RD)由 5 78± 0 14增至 7 87± 0 12kPa (P <0 0 0 1) ;阈压 (TP)、平衡压 (EP)和饱和压 (SP)则分别从 8 34± 0 35 ,12 71± 0 2 5和 2 4 89±0 2 5下降至 6 41± 0 0 9kPa,11 78± 0 2 4kPa ,2 2 5 6± 0 16kPa (P <0 0 1～ 0 0 0 1)。其中RD ,PS和TP的变化呈明显的剂量依赖性。 ( 2 )用KATP通道阻断剂格列苯脲 (glibenclamide,10 μmol/L)预处理后 ,Cro的上述反射效应即被阻断。( 3)先给予腺苷 (adenosine,12 5 μmol/L)则可以加强Cro对压力感受器反射的影响。以上结果表明 ,KATP通道开放剂Cro对大鼠颈动脉窦压力感受器反射有易化作用 ,此作用是由KATP通道开放剂引起窦壁扩张而牵张压力感受器所致     

Renorenal reflexes: neural and functional responses

Evidence supporting the existence of renorenal reflexes is reviewed. Renal mechanoreceptors (MR) and afferent renal nerve fibers are localized in the corticomedullary region and in the wall of the renal pelvis. Stimulating renal MR by increased ureteral pressure (increases UP) or increased renal venous pressure (increases RVP) and renal chemoreceptors (CR) by retrograde ureteropelvic perfusion with 0.9 M NaCl results in increased ipsilateral afferent renal nerve activity (ARNA) in a variety of species. However, renorenal reflex responses to renal MR and CR differ among species. In the dog, stimulating renal MR results in a modest contralateral excitatory renorenal reflex response with contralateral renal vasoconstriction that is integrated at the supraspinal level. Renal CR stimulation is without effect on systemic and renal function. However, in the rat the responses to renal MR and CR stimulation are opposite to those of the dog. Increased ureteral pressure, renal venous pressure, or retrograde ureteropelvic perfusion with 0.9 M NaCl each results in a receptor-specific contralateral inhibitory renorenal reflex response. The afferent limb consists of increased ipsilateral ARNA and the efferent limb of decreased contralateral efferent RNA with contralateral diuresis and natriuresis. The renorenal reflex responses to MR and CR stimulation are integrated at the supraspinal level.     

肾动脉内注射腺苷兴奋肾神经传入纤维的自发活动

应用记录肾神经传入纤维多单位和单位放电的方法,观察肾动脉内注射腺苷对麻醉家兔肾神经传入纤维自发放电活动的影响。结果表明：(1)肾动脉内注射50,100和200nmol／kg腺苷可呈剂量依赖性地兴奋肾神经传入纤维的活动,而动脉血压不变。(2)肾动脉内预先应用选择性腺苷A1受体阻断剂DPCPX(160nmol/kg),可部分阻断腺苷对肾神经传入纤维的兴奋作用。(3)静脉应用一氧化氮合酶抑制剂L-NAME(0．1mmol／kg)预处理,延长并增强了肾神经传入纤维对腺苷的反应。以上结果提示,肾动脉内应用腺苷可兴奋肾传入纤维的自发放电活动,一氧化氮作为抑制性因素参与腺苷诱导的肾神经传入纤维兴奋。     

Renal sympathetic nerve activity modulates afferent renal nerve activity by PGE2-dependent activation of alpha1- and alpha2-adrenoceptors on renal sensory nerve fibers

Increasing efferent renal sympathetic nerve activity (ERSNA) increases afferent renal nerve activity (ARNA). To test whether the ERSNA-induced increases in ARNA involved norepinephrine activating alpha-adrenoceptors on the renal sensory nerves, we examined the effects of renal pelvic administration of the alpha(1)- and alpha(2)-adrenoceptor antagonists prazosin and rauwolscine on the ARNA responses to reflex increases in ERSNA (placing the rat's tail in 49 degrees C water) and renal pelvic perfusion with norepinephrine in anesthetized rats. Hot tail increased ERSNA and ARNA, 6,930 +/- 900 and 4,870 +/- 670%.s (area under the curve ARNA vs. time). Renal pelvic perfusion with norepinephrine increased ARNA 1,870 +/- 210%.s. Immunohistochemical studies showed that the sympathetic and sensory nerves were closely related in the pelvic wall. Renal pelvic perfusion with prazosin blocked and rauwolscine enhanced the ARNA responses to reflex increases in ERSNA and norepinephrine. Studies in a denervated renal pelvic wall preparation showed that norepinephrine increased substance P release, from 8 +/- 1 to 16 +/- 1 pg/min, and PGE(2) release, from 77 +/- 11 to 161 +/- 23 pg/min, suggesting a role for PGE(2) in the norepinephrine-induced activation of renal sensory nerves. Prazosin and indomethacin reduced and rauwolscine enhanced the norepinephrine-induced increases in substance P and PGE(2). PGE(2) enhanced the norepinephrine-induced activation of renal sensory nerves by stimulation of EP4 receptors. Interaction between ERSNA and ARNA is modulated by norepinephrine, which increases and decreases the activation of the renal sensory nerves by stimulating alpha(1)- and alpha(2)-adrenoceptors, respectively, on the renal pelvic sensory nerve fibers. Norepinephrine-induced activation of the sensory nerves is dependent on renal pelvic synthesis/release of PGE(2).     

Activation of renal mechanosensitive neurons involves bradykinin, protein kinase C, PGE(2), and substance P

Increased renal pelvic pressure or bradykinin increases afferent renal nerve activity (ARNA) via PGE(2)-induced release of substance P. Protein kinase C (PKC) activation increases ARNA, and PKC inhibition blocks the ARNA response to bradykinin. We now examined whether bradykinin mediates the ARNA response to increased renal pelvic pressure by activating PKC. In anesthetized rats, the ARNA responses to increased renal pelvic pressure were blocked by renal pelvic perfusion with the bradykinin B(2)-receptor antagonist HOE 140 and the PKC inhibitor calphostin C by 76 +/- 8% (P < 0.02) and 81 +/- 5% (P < 0.01), respectively. Renal pelvic perfusion with 4beta-phorbol 12,13-dibutyrate (PDBu) to activate PKC increased ARNA 27 +/- 4% and renal pelvic release of PGE(2) from 500 +/- 59 to 1, 113 +/- 183 pg/min and substance P from 10 +/- 2 to 30 +/- 2 pg/min (all P < 0.01). Indomethacin abolished the increases in substance P release and ARNA. The PDBu-mediated increase in ARNA was also abolished by the substance P-receptor antagonist RP 67580. We conclude that bradykinin contributes to the activation of renal pelvic mechanosensitive neurons by activating PKC. PKC increases ARNA via a PGE(2)-induced release of substance P.     

Impaired responsiveness of renal mechanosensory nerves in heart failure: role of endogenous angiotensin

Increasing renal pelvic pressure results in PGE(2)-mediated release of substance P. Substance P increases afferent renal nerve activity (ARNA), which leads to a reflex increase in urinary sodium excretion (U(Na)V). Endogenous ANG II modulates the responsiveness of renal mechanosensory nerves. The ARNA and U(Na)V responses are suppressed by low- and enhanced by high-sodium diet. We examined whether the ARNA responses are altered in rats with congestive heart failure (CHF), a condition characterized by increased ANG II and sodium retention. The ARNA responses to increasing renal pelvic pressure 相似文献   

Afferent renal denervation impairs baroreflex control of efferent renal sympathetic nerve activity

Increasing efferent renal sympathetic nerve activity (ERSNA) increases afferent renal nerve activity (ARNA), which decreases ERSNA to prevent sodium retention. High-sodium diet enhances ARNA, suggesting an important role for ARNA in suppressing ERSNA during excess sodium intake. Mean arterial pressure (MAP) is elevated in afferent renal denervated by dorsal rhizotomy (DRX) rats fed high-sodium diet. We examined whether the increased MAP in DRX is due to impaired arterial baroreflex function. In DRX and sham DRX rats fed high-sodium diet, arterial baroreflex function was determined in conscious rats by intravenous nitroprusside and phenylephrine or calculation of transfer function gain from arterial pressure to ERSNA (spontaneous baroreflex sensitivity). Increasing MAP did not suppress ERSNA to the same extent in DRX as in sham DRX, -60 +/- 4 vs. -77 +/- 6%. Maximum gain, -4.22 +/- 0.45 vs. -6.04 +/- 0.90% DeltaERSNA/mmHg, and the maximum value of instantaneous gain, -4.19 +/- 0.45 vs. -6.04 +/- 0.81% DeltaERSNA/mmHg, were less in DRX than in sham DRX. Likewise, transfer function gain was lower in DRX than in sham DRX, 3.9 +/- 0.2 vs. 6.1 +/- 0.5 NU/mmHg. Air jet stress produced greater increases in ERSNA in DRX than in sham DRX, 35,000 +/- 4,900 vs. 20,900 +/- 3,410%.s (area under the curve). Likewise, the ERSNA responses to thermal cutaneous stimulation were greater in DRX than in sham DRX. These studies suggest impaired arterial baroreflex suppression of ERSNA in DRX fed high-sodium diet. There were no differences in arterial baroreflex function in DRX and sham DRX fed normal-sodium diet. Impaired arterial baroreflex function contributes to increased ERSNA, which would eventually lead to sodium retention and increased MAP in DRX rats fed high-sodium diet.     

PGE(2) increases release of substance P from renal sensory nerves by activating the cAMP-PKA transduction cascade

Increasing renal pelvic pressure increases afferent renal nerve activity (ARNA) by a PGE(2)-mediated release of substance P (SP) from renal pelvic nerves. The role of cAMP activation in the PGE(2)-mediated release of SP was studied by examining the effects of the adenylyl cyclase (AC) activator forskolin and AC inhibitor dideoxyadenosine (DDA). Forskolin enhanced the bradykinin-mediated release of SP from an isolated rat renal pelvic wall preparation, from 7.3 +/- 1.3 to 15.6 +/- 3.0 pg/min. PGE(2) at a subthreshold concentration for SP release mimicked the effects of forskolin. The EP(2) receptor agonist butaprost, 15 microM, and PGE(2), 0.14 microM, produced similar increases in SP release, from 5.8 +/- 0.8 to 17.0 +/- 2.3 pg/min and from 8.0 +/- 1.3 to 21.6 +/- 2.7 pg/min. DDA blocked the SP release produced by butaprost and PGE(2). The PGE(2)-induced release of SP was also blocked by the PKA inhibitors PKI(14-22) and H-89. Studies in anesthetized rats showed that renal pelvic administration of butaprost, 10 microM, and PGE(2), 0.14 microM, resulted in similar ARNA responses, 1,520 +/- 390 and 1,170 +/- 270%. s (area under the curve of ARNA vs. time) that were blocked by DDA. Likewise, the ARNA response to increased renal pelvic pressure, 7,180 +/- 710%. s, was blocked by DDA. In conclusion, PGE(2) activates the cAMP-PKA pathway leading to a release of SP and activation of renal pelvic mechanosensory nerve fibers.