Renorenal reflexes: interaction between efferent and afferent renal nerve activity.

In rats, stimulation of renal mechanoreceptors by increasing ureteral pressure results in a contralateral inhibitory renorenal reflex response consisting of increases in ipsilateral afferent renal nerve activity, decreases in contralateral efferent renal nerve activity, and increases in contralateral urine flow rate and urinary sodium excretion. Mean arterial pressure is unchanged. To study possible functional central interaction among the afferent renal nerves and the aortic and carotid sinus nerves, the responses to renal mechanoreceptor stimulation were compared in sinoaortic denervated rats and sham-denervated rats before and after vagotomy. In contrast to sham-denervated rats, there was an increase in mean arterial pressure in response to renal mechanoreceptor stimulation in sinoaortic-denervated rats. However, there were no differences in the renorenal reflex responses among the groups. Thus, our data failed to support a functional central interaction among the renal, carotid sinus, and aortic afferent nerves in the renorenal reflex response to renal mechanoreceptor stimulation. Studies to examine peripheral interaction between efferent and afferent renal nerves showed that marked reduction in efferent renal nerve activity produced by spinal cord section at T6, ganglionic blockade, volume expansion, or stretch of the junction of superior vena cava and right atrium abolished the responses in afferent renal nerve activity and contralateral renal function to renal mechanoreceptor stimulation. Conversely, increases in efferent renal nerve activity caused by thermal cutaneous stimulation increased basal afferent renal nerve activity and its responses to renal mechanoreceptor stimulation. These data suggest a facilitatory role of efferent renal nerves on renal sensory receptors.     

刺激肾神经传入纤维的降压反应与颈动脉窦压力感受性反射的相互作用

在麻醉兔,研究了刺激肾神经传入纤维与颈动脉窦压力感受性反射在减压反射中的相互作用。电刺激肾神经传入纤维引起平均动脉压(MAP)下降,下降程度在一定范围有赖于刺激频率。当颈动脉窦被隔离和主动脉神经切断后,随着颈动脉窦内压逐渐升高,刺激肾神经传入纤维引起的减压反应不断减弱。在45至135mmHg 之间的7个颈动脉窦内压(ISP)水平,刺激肾神经传入纤维,并画出刺激前和刺激时的 ISP-MAP 关系曲线。在颈动脉窦内压为75至105mmHg 之间,刺激肾神经传入纤维显著降低 ISP-MAP 关系曲线的斜率和对ISP 的平均动脉压反应范围。这些结果提示:(1)颈动脉窦压力感受器的传入冲动可调制刺激肾神经传入纤维的降压反应,在一定范围内与颈动脉窦内压呈反比;(2)刺激肾神经传入纤维明显减弱颈动脉窦的压力感受性反射。     

Influence of substance P on carotid sinus nerve baro- and chemoreceptor activity in rabbits.

Substance P (SP) is abundant in the carotid sinus nerve (CSN) and has been implicated in baro- and chemoreceptor reflexes. We examined the effect of SP on blood pressure, heart rate, phrenic nerve activity, hindlimb perfusion pressure, and cardiac contractile strength in urethane-anesthetized rabbits with bilaterally cut cervical sympathetic, vagus, and aortic depressor nerves. Retrograde simultaneous injection of SP (0.5-2.7 micrograms/kg in 0.2-0.3 ml saline) into both carotid sinus areas via the internal carotid arteries decreased blood pressure (by 56%), heart rate (by 13%), cardiac contractility (by 25%) and phrenic nerve activity (by 77%). The effect on hindlimb perfusion pressure was variable. There was both a reflex effect and direct hindlimb vasodilation. In another group of rabbits, the carotid sinus areas were vascularly isolated and perfused with SP (0.19 micrograms/min dissolved in Locke's solution) or Locke's solution alone for 5 min. While carotid sinus perfusion pressure was maintained in the range of 80-120 mmHg, mean arterial blood pressure, heart rate, and unit activity from the CSN were recorded. SP increased the activity of 11 of 18 baroreceptor fibers and inhibited all of 20 chemoreceptor fibers. SP decreased mean arterial blood pressure and heart rate, but the changes were less than those obtained with injection of SP into nonisolated carotid sinus arteries because systemic effects of SP, which in some cases counteracted the reflex effects, were eliminated.     

Left ventricular reflex control of venous return and systemic vascular capacitance in dogs

The reflex effects of left ventricular distension on venous return, vascular capacitance, vascular resistance, and sympathetic efferent nerve activity were examined in dogs anesthetized with sodium pentobarbital. In addition, the interaction of left ventricular distension and the carotid sinus baroreflex was examined. Vascular capacitance was assessed by measuring changes in systemic blood volume, using extracorporeal circulation with constant cardiac output and constant central venous pressure. Left ventricular distension produced by balloon inflation caused a transient biphasic change in venous return; an initial small increase was followed by a late relatively large decrease. Left ventricular distension increased systemic blood volume by 3.8 +/- 0.6 mL/kg and decreased systemic blood pressure by 27 +/- 2 mmHg (1 mmHg = 133.3 Pa) at an isolated carotid sinus pressure of 50 mmHg. These changes were accompanied by a simultaneous decrease in sympathetic efferent nerve activity. When the carotid sinus pressure was increased to 125 and 200 mmHg, these responses were attenuated. It is suggested that left ventricular mechanoreceptors and carotid baroreceptors contribute importantly to the control of venous return and vascular capacitance.     

The ratio of systemic and coronary fractions of left ventricular output in reflex pressor reactions

In acute experiments the participation of coronary and systemic fractions was studied during suppression of the carotid sinus baroreceptors by the occlusion of the carotid arteries and stimulation of the tibial nerve afferent fibers. In most tests systemic fraction was reduced in carotid arteries occlusion and increased in tibial nerve stimulation. The coronary fraction was always increased. The cardiac output (the sum of systemic and coronary fractions) was steady with blood pressure increase by 20 to 70%. The role of coronary fraction in the mechanism of homeometric regulation of the heart is discussed.     

Baroreceptor control of pressure-flow relationships during hypoxemia

In the absence of peripheral chemoreceptors, the effects of graded hypoxemia on the carotid sinus control of central and regional hemodynamics were studied in anesthetized mongrel dogs. Baroreceptor stimulation was effected by carotid sinus isolation and perfusion under controlled pressure. Blood flows were measured in the aorta and the celiac, mesenteric, left renal, and right iliac arteries. Carotid sinus reflex set-point pressures were well maintained until hypoxemia was severe. Carotid sinus reflex set-point gain was maximal during mild hypoxemia. Reflex operating point regional flows were unaffected by hypoxemia. A factorial analysis of overall reflex increases in mean aortic pressure, flow, and power during reduced baroreceptor stimulation showed potentiation by increasing hypoxemia. Corresponding effects of baroreceptor stimulation and hypoxemia on aortic resistance and heart rate were additive. Celiac, renal, and iliac blood flows increased during both hypoxemia and reduced baroreceptor stimulation. Only in the celiac bed were blood flow changes independent of concomitant changes in cardiac output. Thus, at maximum sympathetic stimulation (low carotid sinus pressure) during hypoxemia, the cardiovascular system maintained both central and regional blood flows at high systemic blood pressures independent of the peripheral chemoreceptors.     

Effect of GABA receptor agonist phenibut on behavior and respiration of rabbits in the negative emotional situation

The influence of systemic injection of GABA-receptor agonist--phenibut (40 mg/kg, s/c) on open field behavior, behavioral reactivity and changes in respiratory parameters after exposure of negative emotional stimuli was studied in three rabbit groups differentiated by locomotor activity in open field (active, passive and medium-active animals). The injection of phenibut results in decrease of rabbits horizontal locomotor activity and some components of research behavior in open field and also decrease of behavioral reactivity on emotional stimuli. At the same time the probability of both an active orienting exploratory or defensive reactions and passive reactions (freezing) were decreased. The influence of phenibut depended on typological features of rabbits: the most potent effect occurred upon behavior of active rabbits, less on passive animals and practically none on medium-active rabbits. The phenibut injection results in increase of duration of inhalation during exposure to emotional stimuli, whereas it decreased in normal.     

Effect of fenibut on the GABA B receptors of the spinal motor neurons

It has been established in experiments on the isolated spinal cord of 7-14-day-old rats that the GABAB-mimetic phenibut (10(-5)--10(-4) M) elicits a slow-developing depolarization of motoneurons, suppression of spontaneous activity and polysynaptic reflex discharges of motoneurons, recorded from the ventral roots. Administered under the same conditions GABA produces de- and hyperpolarization of motoneurons. The depolarization of motoneurons elicited by phenibut and GABA is not reversed by picrotoxin in contradistinction to the GABA-induced hyperpolarization of motoneurons, being associated with a direct action of the GABA-mimetics on postsynaptic GABAB receptors of motoneurons. Diazepam (10(-9)--10(-6) M) potentiates the effects of phenibut supposedly via benzodiazepine receptors bound with GABAA receptors (an independent interaction).     

Reflex mechanisms for changes in renal nerve activity during positive end-expiratory pressure

This study was designed to investigate the interaction between carotid sinus baroreceptors and cardiopulmonary receptors in the reflex control of renal nerve activity (RNA) during positive end-expiratory pressure (PEEP) in anesthetized dogs. PEEP at two different levels (10 and 20 cmH2O) was applied to the following groups: animals with neuraxis intact (I group, n = 12); vagal and aortic nerve denervated animals with carotid sinus nerves intact (V group, n = 6); carotid sinus denervated animals with vagal and aortic nerves intact (SD group, n = 6); and carotid sinus denervated animals also having severed vagal and aortic nerves (SAV group, n = 12). Mean blood pressure (MBP), central venous pressure, and mean airway pressure were also simultaneously measured. In the I group, no significant alterations in RNA occurred during PEEP at both levels, even when MBP fell significantly. Although the drop in MBP in the SD group was similar to that in the I group, RNA decreased significantly 10 s after intervention at both PEEP levels, followed by a recovery of RNA toward the control level. In contrast, a significant increase in RNA, which continued until the end of PEEP, appeared in the V group immediately after each intervention. In the SAV group, RNA responses to PEEP, which were observed in the other groups, were abolished. These results provide evidence that during PEEP, renal nerve activity is modified by an interaction between carotid sinus baroreceptors and cardiopulmonary receptors; excitatory effects occur via carotid sinus nerves and inhibitory effects occur via vagal afferents.     

The inhibition of efferent sympathetic activity by means of pressure stimulation of the carotid sinus pressoreceptors]

The influence of pressure stimulation of a barorecptor upon the activity of the sympathetic nerve branch terminating in the wall of the contralateral carotid bifurcation was studied on narcotized dogs. The potential activity of this branch is of efferent nature. On the average, 570 msec after the pressure load applied to the opposite carotid sinus preparation, a silent period occurred. The duration of this silent period and the activity of the sympathetic nerve branch depend on the internal pressure of the preparation. The influence of different structures (central and peripheral) on latency, total and partial inhibition of the sympathetic activity are discussed.     

电刺激猫小脑顶核对动脉血压和肾交感神经放电的影响

在38只麻醉及人工呼吸的猫,观察到电刺激小脑顶核嘴侧部能引起动脉血压显著升高;肾交感神经放电于刺激期间显著增加。去缓冲神经对刺激顶核所引起的血压反应的幅度和肾交感神经放电均无明显影响,但可明显延长血压反应升高相以及血压恢复期的时间。静脉注射氯庄定引起血压降低、心率减慢及肾交感神经放电的抑制,并能减弱刺激顶核引起的血压反应,但增强了刺激顶核引起的肾神经放电的变化。电解损毁延髓腹外侧面引起血压降低及肾交感神经放电的抑制,然而无论单侧还是双侧损毁延髓腹外侧面都不能阻断刺激顶核所引起的血压和肾交感神经放电的反应。以上结果表明,电刺激顶核能引起明显的心血管反应,其反应的下行性通路可能不通过延髓腹外侧面。     

The efferent sympathetic activity of the rabbit renal nerve during local application of adrenaline to the carotid sinus]

Adrenalin solution (1:1000) administered at the carotid sinus, through excitation of the depressoric C-fibre system of the carotid nerve, induces a strong, lasting reflectoric decrease of arterial pressure with slowing heart rate, associated with an almost complete inhibition of the efferent sympathetic activity of the renal nerve. The efferent sympathetic activity, arterial blood pressure and heart rate, both at the onset and at the height of adrenalin action, show corresponding activity changes: the relative inhibition of the sympathetic nerve is strongest correlated with the depressoric blood-pressure effect, while the decrease of heart rate, related to the initial activity, is least pronounced.     

胍丁胺抑制大鼠颈动脉窦压力感受器活动

在麻醉大鼠隔离灌流颈动脉窦区条件下,记录窦神经传入放电,观察胍丁胺（agmatine,Agm)对动脉压力感受器活动的影响,结果如下：（1）以1mmol/L Agm隔离灌流大鼠颈动脉窦区时,窦内压－窦神经传入放电积分（ISP－ISNA）关系曲线向右下方移位,曲线的最大斜率（PS）降低,窦神经传入放电量最大积分值（PIV）减小,再分别以5,10mmol/L Agm灌流时,机能曲线向右下方移位更为明显,PS及PIV降低更加明显,从而表明Agm抑制压力感受器活动且呈剂量依赖性,（2）α2－肾上腺素受体（α2－adrenoceptor,α-AR）和咪唑啉受体（IR）的阻断剂咪唑克生（0．1mmol/L)可阻断Agm的上述效应。（3）预先灌流α-AR能亨宾（15umol/L)可部分阻断Agm的抑制效应。（4）预先灌流Ca^2 通道激动剂Bay K8644(500mmol/L)亦可取消Agm对窦神经传入放电的影响,以上结果表明,Agm对基动脉窦压力感受器活动有抑制作用,此作用由IR和α-AR介导,并与颈动脉窦压力感受器活动时Ca^2 内流减少有关。     

多巴胺对急性间歇性低氧诱导的大鼠颈动脉体低氧敏感性的影响*

目的: 观察急性间歇性低氧刺激后大鼠颈动脉体对低氧的敏感性以及多巴胺对颈动脉体低氧敏感性的影响。方法: 将分离SD大鼠的颈动脉体-窦神经移入到孵育槽,然后把分离的窦神经吸入到记录的玻璃电极中行电信号记录。记录基线部分缓冲液充入气体为95% O₂+ 5% CO₂混合气,低氧应激给予5% O₂+ 5% CO₂+ 90% N₂混合气,低氧刺激给予30 s,95% O₂ + 5% CO₂给予90 s,共10个循环,每组实验大鼠数量n大于等于5。结果: 大鼠离体的颈动脉体,给予急性间歇性低氧应激,再给予低氧刺激,窦神经较之前低氧刺激放电活动增强。但加入多巴胺后,可以抑制窦神经对低氧的反应,急性间歇性低氧后,多巴胺对窦神经的低氧放电活动抑制作用加强。结论: 大鼠颈动脉体给予急性间歇性低氧可增强窦神经对低氧的反应,多巴胺可抑制急性低氧诱导的颈动脉体对低氧敏感性的增强。     

GABA representation in hypoxia sensing: a ventilatory study in the rat

Phenibut, a nonspecific GABA derivative, is clinically used as an anxiolytic and tranquilizer in psychosomatic conditions. A GABA-ergic inhibitory pathway is engaged in respiratory control at both central and peripheral levels. However, the potential of phenibut to affect the O2-related chemoreflexes has not yet been studied. In this study we seek to determine the ventilatory responses to changes in inspired O2 content in anesthetized, spontaneously-breathing rats. Steady-state 5-min responses to 10% O2 in N2 and 100% O2 were taken in each animal before and 1 h after phenibut administration in a dose 450 mg/kg, i.p. Minute ventilation and its frequency and tidal components were obtained from the respiratory flow signal. We found that after a period of irregular extension of the respiratory cycle, phenibut stabilized resting ventilation at a lower level [20.0±3.3 (SD) vs 31.1±5.2 ml/min before phenibut; P<0.01]. The ventilatory depressant effect of phenibut was not reflected in the hypoxic response. In relative terms, this response was actually accentuated after phenibut; the peak hypoxic ventilation increased by 164% from baseline vs the 100% increase before phenibut. Regarding hyperoxia, its inhibitory effect on breathing was more expressed after phenibut. In conclusion, the GABA-mimetic phenibut did not curtail hypoxic ventilatory responsiveness, despite the presence of GABA-ergic pathways in both central and peripheral, carotid body mechanisms mediating the hypoxic chemoreflex. Thus, GABA-mediated synaptic inhibition may be elaborated in a way to sustain the primarily defensive ventilatory chemoreflex.     

Differential role of the paraventricular nucleus of the hypothalamus in modulating the sympathoexcitatory component of peripheral and central chemoreflexes

In the present study we investigated the involvement of the hypothalamic paraventricular nucleus (PVN) in the modulation of sympathoexcitatory reflex activated by peripheral and central chemoreceptors. We measured mean arterial blood pressure (MAP), heart rate (HR), renal sympathetic nerve activity (RSNA), and phrenic nerve activity (PNA) before and after blocking neurotransmission within the PVN by bilateral microinjection of 2% lidocaine (100 nl) during specific stimulation of peripheral chemoreceptors by potassium cyanide (KCN, 75 microg/kg iv, bolus dose) or stimulation of central chemoreceptors with hypercapnia (10% CO(2)). Typically stimulation of peripheral chemoreceptors evoked a reflex response characterized by an increase in MAP, RSNA, and PNA and a decrease in HR. Bilateral microinjection of 2% lidocaine into the PVN had no effect on basal sympathetic and cardiorespiratory variables; however, the RSNA and PNA responses evoked by peripheral chemoreceptor stimulation were attenuated (P < 0.05). Bilateral microinjection of bicuculline (50 pmol/50 nl, n = 5) into the PVN augmented the RSNA and PNA response to peripheral chemoreceptor stimulation (P < 0.05). Conversely, the GABA agonist muscimol (0.2 nmol/50 nl, n = 5) injected into the PVN attenuated these reflex responses (P < 0.05). Blocking neurotransmission within the PVN had no effect on the hypercapnia-induced central chemoreflex responses in carotid body denervated animals. These results suggest a selective role of the PVN in processing the sympathoexcitatory and ventilatory component of the peripheral, but not central, chemoreflex.     

心房钠泵因子对颈动脉窦压力感受器反射的易化作用

Effects of atriopeptin II (APII) on the carotid sinus baroreflex in anesthetized rats and on the sinus nerve afferent activity in the anesthetized rabbits were investigated. The results were as follows: (1) By perfusing the isolated left carotid sinus with APII (1 microgram/ml) in anesthetized rats (n = 10), the threshold pressure (TP) of the carotid baroreflex did not show any change, while the equilibrium pressure (EP), the saturation pressure (SP) and the operating range (OR) were decreased from 101 +/- 2.8 to 95 +/- 2.0 mmHg (P less than 0.05), 202 +/- 5.2 to 168 +/- 6.1 mmHg (P less than 0.001) and 128 +/- 5.5 to 93 +/- 6.3 mmHg (P less than 0.001), respectively. The function curve of the baroreflex was shifted to the left and downward with a peak slope (PS) increased during perfusing with APII. In contrast, by perfusing the carotid sinus with sodium nitroprusside (NP, 0.5 micrograms/ml), TP and EP remained unchanged, whereas SP and OR were increased from 188 +/- 6.4 to 218 +/- 6.0 mmHg (n = 6, P less than 0.01) and from 107 +/- 6.9 to 132 +/- 7.6 mmHg (P less than 0.05), respectively. The function curve of the baroreflex and its PS were not affected by NP. The sinus nerve afferent activity was quite stable with the perfusion of carotid sinus at constant intrasinus pressure (ISP) in the rabbits (n = 6) and increased during the elevation of ISP.(ABSTRACT TRUNCATED AT 250 WORDS)     

腺苷易化大鼠颈动脉窦压力感受器的活动

在36只麻醉大鼠,以隔离灌流颈动脉窦区记录窦神经传入放电的方法观察了腺苷（adenosine,Ado）对颈动脉窦压力感受器传入放电的影响。所得结果如下：（1）以75μmol／LAdo隔离灌流大鼠左侧颈动脉窦区时,窦内压-窦神经传入放电积分（ISP－ISNA）关系曲线向左上方移位,曲线最大斜率（PS）由（18．75±0．12）％／kPa增至（22．21±0．11）％／kPa（P＜0．001）,最大积分值（PIV）由（209．83±2．57）％增至（239．17±1．75）％;阈压（TP）和饱和压（SP）则分别从（8．57±0．24）和（22．99±0．34）下降至（7．15±0．23）kPa（P＜0．001）和（21．21±0,43）kPa（P＜0．01）。再分别以125和175μmol／LAdo灌流,机能曲线进一步向左上方移位,PS、TP和SP的变化均呈明显的剂量依赖性。（2）用腺苷选择性A1受体拮抗剂8－cyclopentyl－1,3－dipropylxanthine（0．134mmol／L）预处理后,Ado的上述效应即被阻断。（3）先给予KATP通道阻断剂格列苯脲（10μmol／L）亦可取消腔苷对窦神经传入放电的影响。结果表明,在体隔离灌流大鼠颈动脉窦区条件下,Ado对颈动脉窦压力感受器活动有易化作用,此作用似与腺苷A1受体介导的KATP通道开放有关。     

Plasma vasopressin response to haemorrhage in the anaesthetized rabbit

In chloralose-urethane anaesthetized rabbits the acute circulatory and plasma vasopressin (pAVP) responses to moderate haemorrhage of 6 mL/kg body weight (10% blood volume) were followed after serial section of the aortic, vagus, and carotid sinus nerves. With all nerves intact, haemorrhage resulted in significant increases in pAVP, accompanied by decreases in systemic arterial pressure and right atrial pressure. With subsequent section of each afferent nerve, pAVP still increased in response to haemorrhage regardless of the order of nerve section. These results suggest that, in the anaesthetized rabbit, there is a further component of the pAVP response to haemorrhage, in addition to those carried in the aortic, vagus, and carotid sinus nerves.     

Central antihypertensive properties of muscimol and related gamma-aminobutyric acid agonists and the interaction of muscimol with baroreceptor reflexes.

The central antihypertensive properties of four gamma-aminobutyric acid (GABA) analogs were characterized in anesthetized cats with implanted intracerebroventricular cannulae. An intracerebroventricular infusion (icv) of muscimol, 0.1--0.5 microgram/min (total dose: 1--5 micrograms, icv), substantially reduced mean arterial pressure and slightly reduced heart rate. The compound was not hypotensive at 5 micrograms, iv (total dose) and only slightly hypotensive after an intracisternal injection (5 micrograms). Kojic amine (2-aminomethyl-5-hydroxy-4H-pyran-4-one) and baclofen were also hypotensive following an intracerebroventricular infusion, but they were less active than muscimol. GABA, at 15--150 micrograms/min, icv (total dose, 150--1500 micrograms, icv), was not hypotensive by itself and unlike muscimol its activity was not enhanced in cats pretreated with nipecotic acid, an uptake inhibitor of GABA. The ability of muscimol to interfere with baroreceptor reflexes was considered in experiments in which reflex vasoconstrictor (carotid occlusion) and reflex vasodilatation (acute elevation in mean arterial pressure with norepinephrine) was measured in the perfused hindlimb of cats previously prepared with intracerebroventricular cannulae. Muscimol significantly attenuated the response to bilateral carotid occlusion and completely abolished reflex vasodilatation. The results suggest that GABA agonists and analogs may regulate blood pressure centrally and, through an interaction with the central nervous system, may attenuate baroreceptor reflexes.