Afferent mechanisms underlying stimulation modality-related modulation of acupuncture-related cardiovascular responses.

Despite the use of acupuncture to treat a number of heart diseases, little is known about the mechanisms that underlie its actions. Therefore, we examined the influence of acupuncture on sympathoexcitatory cardiovascular responses to gastric distension in anesthetized Sprague-Dawley rats. Thirty minutes of low-current, low-frequency, (0.3-0.5 mA, 2 Hz) electroacupuncture (EA), at P 5-6, S 36-37, and H 6-7 overlying the median, deep peroneal, and ulnar nerves significantly decreased reflex pressor responses by 40, 39, and 44%, respectively. In contrast, sham acupuncture involving needle insertion without stimulation at P 5-6 or 30 min of EA at LI 6-7 acupoints overlying the superficial radial nerve did not attenuate the reflex. Similarly, EA at P 5-6 using 40- or 100-Hz stimulation frequencies did not inhibit the reflex. Compared with EA at P 5-6, EA at two sets of acupoints, including P 5-6 and S 36-37, did not lead to larger inhibition of the reflex. Two minutes of manual acupuncture (MA; 2 Hz) at P 5-6 every 10 min for 30 min inhibited the reflex cardiovascular pressor response by 33%, a value not significantly different from 2-Hz EA at P 5-6. Single-unit afferent activity was not different between electrical stimulation (ES) and manual stimulation. However, 2-Hz ES activated more somatic afferents than 10- or 20-Hz ES. These data suggest that, although the location of acupoint stimulation and the frequency of stimulation determine the extent of influence of EA, there is little difference between low-frequency EA and MA at P 5-6. Furthermore, simultaneous stimulation using two acupoints that independently exert strong effects did not lead to an additive or a facilitative interaction. The similarity of the responses to EA and MA and the lack of cardiovascular response to high-frequency EA appear to be largely a function of somatic afferent responses.     

Modulation of cardiovascular excitatory responses in rats by transcutaneous magnetic stimulation: role of the spinal cord.

This study investigated the efficacy of magnetic stimulation on the reflex cardiovascular responses induced by gastric distension in anesthetized rats and compared these responses to those influenced by electroacupuncture (EA). Unilateral magnetic stimulation (30% intensity, 2 Hz) at the Jianshi-Neiguan acupoints (pericardial meridian, P 5-6) overlying the median nerve on the forelimb for 24 min significantly decreased the reflex pressor response by 32%. This effect was noticeable by 20 min of magnetic stimulation and continued for 24 min. Median nerve denervation abolished the inhibitory effect of magnetic stimulation, indicating the importance of somatic afferent input. Unilateral EA (0.3-0.5 mA, 2 Hz) at P 5-6 using similar durations of stimulation similarly inhibited the response (35%). The inhibitory effects of EA occurred earlier and were marginally longer (20 min) than magnetic stimulation. Magnetic stimulation at Guangming-Xuanzhong acupoints (gallbladder meridian, GB 37-39) overlying the superficial peroneal nerve on the hindlimb did not attenuate the reflex. Intravenous naloxone immediately after termination of magnetic stimulation reversed inhibition of the cardiovascular reflex, suggesting involvement of the opioid system. Also, intrathecal injection of delta- and kappa-opioid receptors antagonists, ICI174,864 (n=7) and nor-binaltorphimine (n=6) immediately after termination of magnetic stimulation reversed inhibition of the cardiovascular reflex. In contrast, the mu-opioid antagonist CTOP (n=7) failed to alter the cardiovascular reflex. The endogenous neurotransmitters for delta- and kappa-opioid receptors, enkephalins and dynorphin but not beta-endorphin, therefore appear to play significant roles in the spinal cord in mediating magnetic stimulation-induced modulation of cardiovascular reflex responses.     

Excitatory projections from arcuate nucleus to ventrolateral periaqueductal gray in electroacupuncture inhibition of cardiovascular reflexes

We have shown that the modulatory effect of electroacupuncture (EA) on the blood pressure (BP) response induced by visceral organ stimulation is related to inhibition of cardiovascular neurons in the rostral ventrolateral medulla (rVLM) through a mechanism that involves opioids. This effect is long lasting and may involve a long-loop neural supraspinal pathway, including the arcuate nucleus (ARC), which is an important site of opioid neurotransmitter synthesis. Therefore, we evaluated the role of the hypothalamic ARC and its interaction with the midbrain ventrolateral periaqueductal gray (vlPAG) in the EA-BP response. The gallbladder of alpha-chloralose-anesthetized cats was stimulated to test for the influence of EA on splanchnic afferent-induced cardiovascular reflexes. Electrodes were placed around the splanchnic nerve (SN), and acupuncture needles were applied at P5-6 acupoints overlying the median nerve (MN). Electrophysiological recordings showed that spontaneous activity of ARC and vlPAG neurons was low (1.3 +/- 0.5 and 2.0 +/- 0.5 spikes/s, respectively). We observed a gradation of responses of ARC neurons to the stimulation of different acupoints, ranging from uniform responses of all neurons during stimulation of the P5-6, LI4-11, H5-6, and St2-G2 located over deep nerves to fewer responses during stimulation of LI6-7 and G37-39 located over superficial nerves. Microinjection of the excitatory amino acid dl-homocysteic acid (DLH 4 nM, 50 nl) into the ARC augmented the responses of vlPAG neurons, whereas microinjection of kainic acid (KA 1 mM, 50 nl) to deactivate neurons in the ARC decreased vlPAG responses to SN stimulation. Thirty minutes of EA at P5-6 increased the SN-evoked discharge of vlPAG neurons (7.0 +/- 1.2 to 14.3 +/- 3.0 spikes/30 stimuli), a response that was blocked by microinjection of KA into the ARC. Microinjection of DLH into the ARC, like EA, inhibited (30 min) the reflex increase in BP induced by application of bradykinin (BK) to the gallbladder, whereas microinjection of KA into the ARC blocked the inhibitory influence of EA at P5-6 on the BK-induced BP response. These results suggest that excitatory projections from the ARC to the vlPAG are essential to the EA inhibition of the reflex increase in BP induced by SN or gallbladder visceral afferent stimulation.     

Role of glutamate in the rostral ventrolateral medulla in acupuncture-related modulation of visceral reflex sympathoexcitation

Visceral sympathoexcitatory reflexes induced by stimulation of the gallbladder with bradykinin (BK) are attenuated by electroacupuncture (EA) at Neiguan-Jianshi (P5-6) acupoints located over the median nerve. Previous studies have shown that neurons in the rostral ventrolateral medulla (rVLM) receive convergent input from visceral organs and somatic nerves (activated by EA). Glutamate (Glu), an important excitatory neurotransmitter in the rVLM, processes visceral sympathoexcitatory cardiovascular reflexes. In the present study, we determined the relation between EA-mediated opioidergic modulation of visceral cardiovascular responses and Glu. Reflex cardiovascular responses were evoked by application of BK to the gallbladder before and after EA in anesthetized cats. Glu concentrations ([Glu]) were measured by HPLC from samples collected by microdialysis probe(s) inserted unilaterally or bilaterally into the rVLM. BK-induced reflex responses and [Glu] were attenuated by 45% and 70%, respectively, after 30 min of EA (n = 6). EA alone did not change [Glu] in the rVLM (n = 6, P > 0.05). However, microdialysis of naloxone (100 mM) into the rVLM reversed EA-related inhibition of blood pressure and [Glu] (n = 5). Immunohistochemical visualization showed that delta-opioid receptors colocalized with, and were in close apposition to, vesicular Glu transporter 3- and c-Fos-double-labeled perikarya and processes of rVLM neurons after gallbladder stimulation with BK. These data suggest that EA attenuates BK-induced visceral sympathoexcitatory reflexes through opioid-mediated inhibition of Glu's action in the rVLM.     

Role of medullary GABA, opioids, and nociceptin in prolonged inhibition of cardiovascular sympathoexcitatory reflexes during electroacupuncture in cats

Electroacupuncture (EA) causes prolonged suppression of reflex elevations in blood pressure for 1-2 h in anesthetized preparations. A long-loop pathway involving the arcuate nucleus (ARC), ventrolateral periaqueductal gray, and rostral ventrolateral medulla (rVLM) is involved in sympathoinhibitory cardiovascular EA effects. However, the mechanisms and locations of the prolonged EA inhibition are unknown. We hypothesized that this effect is mediated through a long-loop pathway involving opioid, nociceptin, and gamma-aminobutyric acid (GABA) receptor activation in the rVLM. In anesthetized, ventilated cats application of bradykinin to the gallbladder every 10 min induced consistent reflex increases in blood pressure. Bilateral EA stimulation at the cardiovascular acupoints P5-6 overlying the median nerves reduced the reflex responses for at least 80 min. Bilateral blockade with kynurenic acid in the ARC 60 min after onset of EA inhibition reversed the cardiovascular response, suggesting a role for the ARC in the long-loop pathway during the prolonged inhibitory response. Unilateral microinjection with either an opioid or a GABA(A) antagonist in rVLM 50-60 min after the beginning of the EA response reversed EA inhibition of the cardiovascular excitatory reflex. Gabazine also reversed EA inhibition of cardiovascular premotor sympathetic rVLM neurons. Conversely, microinjection of a nociceptin/orphanin FQ peptide antagonist did not affect the prolonged inhibitory effect. Thus the ARC, an important component in the long-loop pathway in the EA cardiovascular response, is required for prolonged suppression of reflex cardiovascular excitatory responses by EA. Furthermore, in the rVLM, opioids and GABA, but not nociceptin, participate in the long-term EA-related inhibition of sympathoexcitatory cardiovascular responses.     

Brain stem mechanisms underlying acupuncture modality-related modulation of cardiovascular responses in rats.

The present study was designed to investigate brain stem responses to manual acupuncture (MA) and electroacupuncture (EA) at different frequencies at pericardial P (5-6) acupoints located over the median nerve. Activity of premotor sympathetic cardiovascular neurons in the rostral ventral lateral medulla (rVLM) was recorded during stimulation of visceral and somatic afferents in ventilated anesthetized rats. We stimulated either the splanchnic nerve at 2 Hz (0.1-0.4 mA, 0.5 ms) or the median nerve for 30 s at 2, 10, 20, 40, or 100 Hz using EA (0.3-0.5 mA, 0.5 ms) or at approximately 2 Hz with MA. Twelve of 18 cells responsive to splanchnic and median nerve stimulation could be antidromically driven from the intermediolateral columns of the thoracic spinal cord, T2-T4, indicating that they were premotor sympathetic neurons. All 18 neurons received baroreceptor input, providing evidence of their cardiovascular sympathoexcitatory function. Evoked responses during stimulation of the splanchnic nerve were inhibited by 49 +/- 6% (n = 7) with EA and by 46 +/- 4% (n = 6) with MA, indicating that the extent of inhibitory effects of the two modalities were similar. Inhibition lasted for 20 min after termination of EA or MA. Cardiovascular premotor rVLM neurons responded to 2-Hz electrical stimulation at P 5-6 and to a lesser extent to 10-, 20-, 40-, and 100-Hz stimulation (53 +/- 10, 16 +/- 2, 8 +/- 2, 2 +/- 1, and 0 +/- 0 impulses/30 stimulations, n = 7). These results indicate that rVLM premotor sympathetic cardiovascular neurons that receive convergent input from the splanchnic and median nerves during low-frequency EA and MA are inhibited similarly for prolonged periods by low-frequency MA and EA.     

Effect of electroacupuncture on pressor reflex during gastric distension

The effect of electroacupuncture (EA) on the reflex cardiovascular response induced by mechanical distension of the stomach was studied in ventilated male Sprague-Dawley rats anesthetized by ketamine and alpha-chloralose. Repeated balloon inflation of the stomach to produce 20 mmHg tension on the gastric wall induced a consistent rise in mean arterial pressure, while heart rate (372 +/- 22 beats/min) was unchanged. This response was reversed by transection of the splanchnic nerves. Bilateral application of EA (1-2 mA, 2 Hz) at Neiguan-Jianshi acupoints (pericardial meridian, Pe 5-6) over the median nerve for 30 min significantly decreased the pressor response from 33 +/- 6 to 18 +/- 4 mmHg (n = 7, P < 0.05). This effect began after 10 min of EA and continued for 40 min after termination of EA. EA at Zusanli-Shangquxu acupoints (stomach meridian, St 36-37) over the deep peroneal nerve similarly inhibited the pressor response. The effect lasted for 10 min after EA was stopped (n = 6, P < 0.05), while EA at Guangming-Xuanzhong acupoints (gallbladder meridian, GB 37-39) over the superficial peroneal nerve did not inhibit the pressor response. Naloxone injected intravenously (n = 6) immediately after termination of EA or administered by microinjection into the rostral ventrolateral medulla (rVLM) 25 min after initiation of EA (n = 6) reversed the inhibition by EA, suggesting an opiate mechanism, including the rVLM, was involved.     

Midbrain vlPAG inhibits rVLM cardiovascular sympathoexcitatory responses during electroacupuncture

The periaqueductal gray (PAG) is an important integrative region in the regulation of autonomic outflow and cardiovascular function and may serve as a regulatory center as part of a long-loop pathway during somatic afferent stimulation with acupuncture. Because the ventrolateral PAG (vlPAG) provides input to the rostral ventrolateral medulla (rVLM), an important area for electroacupuncture (EA) regulation of sympathetic outflow, we hypothesized that the vlPAG plays a role in the EA-related modulation of rVLM premotor sympathetic neurons activated during visceral afferent stimulation and autonomic excitatory reflexes. Cats were anesthetized and ventilated, and heart rate and mean blood pressure were monitored. Stimulation of the splanchnic nerve by a pledget of filter paper soaked in bradykinin (BK, 10 mug/ml) every 10 min on the gallbladder induced consistent cardiovascular reflex responses. Bilateral stimulation with EA at acupoints over the pericardial meridian (P5-6) situated over the median nerve reduced the increases in blood pressure from 34 +/- 3 to 18 +/- 5 mmHg for a period of time that lasted for 60 min or more. Unilateral inactivation of neuronal activity in the vlPAG with 50-75 nl of kainic acid (KA, 1 mM) restored the blood pressure responses from 18 +/- 3 to 36 +/- 5 mmHg during BK-induced gallbladder stimulation, an effect that lasted for 30 min. In the absence of EA, unilateral microinjection of the excitatory amino acid dl-homocysteic acid (DLH, 4 nM) in the vlPAG mimicked the effect of EA and reduced the reflex blood pressure responses from 35 +/- 6 to 14 +/- 5 mmHg. Responses of 21 cardiovascular sympathoexcitatory rVLM neurons, including 12 that were identified as premotor neurons, paralleled the cardiovascular responses. Thus splanchnic nerve-evoked neuronal discharge of 32 +/- 4 spikes/30 stimuli in six neurons was reduced to 10 +/- 2 spikes/30 stimuli by EA, which was restored rapidly to 28 +/- 4 spikes/30 stimuli by unilateral injection of 50 nl KA into the vlPAG. Conversely, 50 nl of DLH in the vlPAG reduced the number of action potentials of 5 rVLM neurons from 30 +/- 4 to 18 +/- 4 spikes/30 stimuli. We conclude that the inhibitory influence of EA involves vlPAG stimulation, which, in turn, inhibits rVLM neurons in the EA-related attenuation of the cardiovascular excitatory response during visceral afferent stimulation.     

Nociceptin in rVLM mediates electroacupuncture inhibition of cardiovascular reflex excitatory response in rats.

Electroacupuncture (EA) at Neiguan-Jianshi acupoints through an opioid mechanism inhibits the cardiovascular pressor response induced by mechanical stimulation of the stomach. Because nociceptin also may regulate cardiovascular activity through its action in the brain stem, we hypothesized that this neuromodulator serves a role in the EA-related inhibitory effect. Blood pressure in ventilated male Sprague-Dawley rats (400-600 g) anesthetized by ketamine and alpha-chloralose was measured during balloon inflation of the stomach. Gastric distension with 6-8 ml of air induced consistent pressor reflexes of 26 +/- 1 mmHg that could be repeated every 10 min for 100 min. When nociceptin (10 nM) was microinjected into the rostral ventrolateral medulla (rVLM), the pressor response induced by gastric distension was inhibited by 68 +/- 6%. Thirty minutes of EA also decreased the reflex response by 75 +/- 11%; microinjection of saline into the rVLM did not alter the inhibitory effect of EA. In contrast, microinjection of a nociceptin receptor antagonist into the rVLM promptly reversed the EA response. Pretreatment with the opioid receptor antagonist naloxone did not influence the EA-like inhibitory effect of nociceptin on the distension-induced pressor reflex (22 +/- 1 to 8 +/- 2 mmHg). Furthermore, a mu-opioid receptor agonist microinjected into the rVLM after microinjection of a nociceptin receptor antagonist during EA promptly reversed the nociceptin receptor antagonist-related inhibition of the EA effect. Thus, in addition to the classical opioid system, nociceptin, through opioid receptor-like-1 receptor stimulation in the rVLM, participates in the modulatory influence of EA on reflex-induced increases in blood pressure.     

Modulation of cardiopulmonary depressor reflex in nucleus ambiguus by electroacupuncture: roles of opioids and γ-aminobutyric acid

Stimulation of cardiopulmonary receptors with phenylbiguanide (PBG) elicits depressor cardiovascular reflex responses, including decreases in blood pressure and heart rate mediated in part by the brain stem parasympathetic cardiac neurons in the nucleus ambiguus (NAmb). The present study examined NAmb neurotransmitter mechanisms underlying the influence of electroacupuncture (EA) on the PBG-induced hypotension and bradycardia. We hypothesized that somatic stimulation during EA modulates PBG responses through opioid and γ-aminobutyric acid (GABA) modulation in the NAmb. Anesthetized and ventilated cats were studied during repeated stimulation with PBG or cardiac vagal afferents while low-frequency EA (2 Hz) was applied at P5-6 acupoints overlying the median nerve for 30 min and NAmb neuronal activity, heart rate, and blood pressure were recorded. Microinjection of kainic acid into the NAmb attenuated the PBG-induced bradycardia from -60 ± 11 to -36 ± 11 beats/min. Likewise, EA reduced the PBG-induced depressor and bradycardia reflex by 52 and 61%, respectively. Cardiac vagal afferent evoked preganglionic cellular activity in the NAmb was reduced by EA for about 60 min. Blockade of opioid or GABA(A) receptors using naloxone and gabazine reversed the EA-related modulation of the evoked cardiac vagal activity by 73 and 53%, respectively. Similarly, naloxone and gabazine reversed EA modulation of the negative chronotropic responses from -11 ± 5 to -23 ± 6 and -13 ± 4 to -24 ± 3 beats/min, respectively. Thus EA at P5-6 decreases PBG evoked hypotension and bradycardia as well as the NAmb PBG-sensitive preganglionic cardiac vagal outflow through opioid and GABA neurotransmitter systems.     

Role of glutamate in a visceral sympathoexcitatory reflex in rostral ventrolateral medulla of cats

The rostral ventrolateral medulla (rVLM) is involved in processing visceral sympathetic reflexes. However, there is little information on specific neurotransmitters in this brain stem region involved in this reflex. The present study investigated the importance of glutamate and glutamatergic receptors in the rVLM during gallbladder stimulation with bradykinin (BK), because glutamate is thought to function as an excitatory neurotransmitter in this region. Stimulation of visceral afferents activated glutamatergic neurons in the rVLM, as noted by double-labeling with c-Fos and the cellular vesicular glutamate transporter 3 (VGLUT3). Visceral reflex activation significantly increased arterial blood pressure as well as extracellular glutamate concentrations in the rVLM as determined by microdialysis. Barodenervation did not alter the release of glutamate in the rVLM evoked by visceral reflex stimulation. Iontophoresis of glutamate into the rVLM enhanced the activity of sympathetic premotor cardiovascular rVLM neurons. Also, the responses of these neurons to visceral afferent stimulation with BK were attenuated significantly (70%) by blockade of glutamatergic receptors with kynurenic acid. Microinjection of either an N-methyl-D-aspartate (NMDA) receptor antagonist 2-amino-5-phosphonopentanate (25 mM, 30 nl) or an dl-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (2 mM, 30 nl) into the rVLM significantly attenuated the visceral sympathoexcitatory reflex responses. These results suggest that glutamate in the rVLM serves as an excitatory neurotransmitter through a baroreflex-independent mechanism and that both NMDA and AMPA receptors mediate the visceral sympathoexcitatory reflex responses.     

Central and peripheral mechanisms underlying gastric distention inhibitory reflex responses in hypercapnic-acidotic rats

We have observed that in chloralose-anesthetized animals, gastric distension (GD) typically increases blood pressure (BP) under normoxic normocapnic conditions. However, we recently noted repeatable decreases in BP and heart rate (HR) in hypercapnic-acidotic rats in response to GD. The neural pathways, central processing, and autonomic effector mechanisms involved in this cardiovascular reflex response are unknown. We hypothesized that GD-induced decrease in BP and HR reflex responses are mediated during both withdrawal of sympathetic tone and increased parasympathetic activity, involving the rostral (rVLM) and caudal ventrolateral medulla (cVLM) and the nucleus ambiguus (NA). Rats anesthetized with ketamine and xylazine or α-chloralose were ventilated and monitored for HR and BP changes. The extent of cardiovascular inhibition was related to the extent of hypercapnia and acidosis. Repeated GD with both anesthetics induced consistent falls in BP and HR. The hemodynamic inhibitory response was reduced after blockade of the celiac ganglia or the intraabdominal vagal nerves with lidocaine, suggesting that the decreased BP and HR responses were mediated by both sympathetic and parasympathetic afferents. Blockade of the NA decreased the bradycardia response. Microinjection of kainic acid into the cVLM reduced the inhibitory BP response, whereas depolarization blockade of the rVLM decreased both BP and HR inhibitory responses. Blockade of GABA(A) receptors in the rVLM also reduced the BP and HR reflex responses. Atropine methyl bromide completely blocked the reflex bradycardia, and atenolol blocked the negative chronotropic response. Finally, α(1)-adrenergic blockade with prazosin reversed the depressor. Thus, in the setting of hypercapnic-acidosis, a sympathoinhibitory cardiovascular response is mediated, in part, by splanchnic nerves and is processed through the rVLM and cVLM. Additionally, a vagal excitatory reflex, which involves the NA, facilitates the GD-induced decreases in BP and HR responses. Efferent chronotropic responses involve both increased parasympathetic and reduced sympathetic activity, whereas the decrease in BP is mediated by reduced α-adrenergic tone.     

Synchronization of respiratory frequency by somatic afferent stimulation.

In cats anesthetized with chloralose-urethan, vagotomized, paralyzed, and artifically ventilated, superficial radial (cutaneous) and hamstring (muscle) nerve afferents were stimulated while phrenic nerve electrical activity was recorded. The results obtained with both types of nerves were similar. Stimulation in mid and late expiration advanced the onset of the next inspiration, shortening its duration. Stimulation in early inspiration advanced, while that in late inspiration delayed, the onset of the next expiration. These effects were often accompanied by changes in phrenic motoneuron firing patterns (earlier recruitment, increased discharge frequency, increased slope of integrated phrenic neurogram). Repetitive somatic afferent stimulation produced sustained increases in respiratory frequency in all cats and in half of them entrainment of respiratory frequency to the frequency of stimulation occurred at ratios such as 4:3, 4:5, 1:2, 1:3, 1:4, and 1:7. The lowest stimulus intensity required for evoking these phase shifts was between 5 and 10T (threshold of most excitable fibers) for muscle afferents and between 1 and 2T for cutaneous afferents. These results demonstrate the existence of a reflex mechanism capable of locking respiratory frequency to that of a periodic somatic afferent input. They also provide an experimental basis for the hypothesis that reflexes are resposible for the observed locking between step or pedal frequency and respiratory rate during exercise in man.     

盆神经和阴部神经传入在大鼠腰骶髓的相互作用

应用条件－检验刺激技术观察时间依赖性抑制现象是研究传入信息相互作用的方式之一。用１．５－３倍阈刺激强度的电脉冲交替刺激麻醉、麻痹的盆神经（Ｐｅ）和阴部神经（Ｐｕ）,以玻璃微电极在Ｌ６－Ｓ１节段脊髓背角会聚神经元上记录细胞外放电。条件输入可对深层（＞３００μｍ）单位的检验反应产生时间依赖性抑制效应,产生抑制的刺激间期为１－３６０ｍｓ,Ｐｅ为条件刺激时较长。浅层细胞（＜３００μｍ）发生抑制的间期为１－     

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.     

Baroreceptor influence on a spinal cardiovascular reflex

A stretch of the walls of the thoracic aorta, performed in vagotomized cats without obstructing aortic flow, induces increases in heart rate, myocardial contractility, and arterial pressure. These reflex responses are still present after high spinal section. Cats under chloralose-urethane anesthesia were vagotomized and one carotid sinus was isolated and perfused with arterial blood at constant flow. The contralateral carotid sinus nerve and both aortic nerves were sectioned. A stretch of the walls of the thoracic aorta between the 7th and 10th intercostal arteries induced a reflex increase in mean arterial pressure 29 +/- 2 mmHg (mean +/- SE). Stepwise increases of carotid sinus pressure (CSP) or electrical stimulation of the carotid sinus nerve induced stepwise decreases of this reflex response. At maximal baroreceptor stimulation (CSP 212 +/- 9 mmHg) the reflex response to aortic stretch was reduced by 42%. These experiments show that this spinal cardiovascular reflex is at least partially under the inhibitory control of the baroreceptor input.     

Efferent activity in the phrenic nerve during startle reflex in chloralose anesthetized cats

Efferent activity was investigated in the phrenic nerve during startle reflex manifesting as somatic nerve discharges (lower intercostal nerves and the nerve endings) in chloralose anesthetized cats. Inhibition (usually of short duration, lasting 23–36 msec) of inspiration activity was found to be the main component of response in the phrenic nerve in the shaping of "low threshold" startle reflex produced by acoustic and tactile stimuli and stimulation of low threshold peripheral afferents. Reflex discharge prevailed amongst the response patterns produced in the phrenic nerve by stimulating high threshold afferents, i.e., early (propriospinal) and late (suprasegmental, arising from stimulating intercostal nerve) or late only (when stimulating the hindlimb nerves). Two patterns of late response could be distinguished, one on inspiration (found in roughly 3 out of 4 experiments) and other on exhalation — the respiratory homologs of somatic startle reflex. Response pattern is described throughout the respiratory cycle. Structure and respiratory modulation of reflex responses produced in the phrenic nerve by stimulating bulbar respiratory structure are also examined. Possible neurophysiological mechanisms underlying phrenic response during the shaping of startle reflex are discussed.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 19, No. 4, pp. 473–482, July–August, 1987.     

Interaction between segmental and descending intersegmental reflexes in lumbar motoneurons

The effects of segmental reflexes on descending intersegmental reflexes to stimulation of forelimb afferents were studied in anesthetized cats by recording postsynaptic responses from single motoneurons. Interaction between these influences was found to be reciprocal in character for groups of neurons with primary connections with afferents of the superficial and deep branches of the peroneal nerve and afferents of the nerve to the gastrocnemius muscle. Excitatory postsynaptic responses arising in groups of motoneurons of the peroneal nerve to stimulation of forelimb afferents underwent profound and prolonged inhibition during conditioning stimulation of afferents in the deep and superficial peroneal nerves. Activation of segmental afferents during conditioning stimulation of the gastrocnemius nerve was accompanied by inhibition of excitatory intersegmental responses and deinhibition of inhibitory responses in motoneurons of the gastrocnemius muscle. Segmental inhibition of intersegmental descending impulse activity appeared in the interneuron system of the segmental reflex centers connecting the descending propriospinal tracts with the motoneurons of these centers.I. P. Pavlov Institute of Physiology, Academy of Sciences of the USSR, Leningrad. Translated from Neirofiziologiya, Vol. 4, No. 2, pp. 16872-175, March–April, 1972.     

Maturation of central autonomic control of the circulation

Postnatal maturation of central neural regulation of cardiovascular function is being examined in developing swine. Three major types of investigations have been undertaken: 1) alterations of inputs from visceral and somatic afferents, e.g., baroreceptor manipulation, stimulation of sciatic nerves; 2) stimulation of central vasoactive sites; 3) subjecting the animals to the stresses of hemorrhage, hypoxia, or hypercapnia. Our findings indicate that cardiovascular reflexes mature at different postnatal ages. For example, the J-receptor reflex had almost the adult pattern of response at birth, whereas the Bezold-Jarisch reflex had a markedly delayed postnatal maturation. Recordings of spontaneous discharge in a major efferent sympathetic supply, i.e., the greater splanchnic nerve, have indicated that neural innervation to the adrenal medulla and splanchnic vasculature is present at birth in piglets.     

Neuronal application of capsaicin modulates somatic pressor reflexes

Static contraction of skeletal muscle elicits a reflex increase in cardiovascular function. Likewise, noxious stimuli activate somatic nociceptors eliciting a reflex increase in cardiovascular function. On the basis of recent work involving spinothalamic cells in the dorsal horn, we hypothesized that the dorsal horn cells involved in the aforementioned reflexes would be sensitized by applying capsaicin (Cap) to a peripheral nerve. If correct, then Cap would enhance the cardiovascular increases that occur when these reflexes are evoked. Cats were anesthetized, and the popliteal fossa was exposed. Static contraction was induced by electrical stimulation of the tibial nerve at an intensity that did not directly activate small-diameter muscle afferent fibers, whereas nociceptors were stimulated by high-intensity stimulation (after muscle paralysis) of either the saphenous nerve (cutaneous nociceptors) or a muscular branch of the tibial nerve (muscle nociceptors). The reflex cardiovascular responses to these perturbations (contraction or nociceptor stimulation) were determined before and after direct application of Cap (3%) onto the common peroneal nerve, using a separate group of cats for each reflex. Compared with control, application of Cap attenuated the peak change in mean arterial pressure (MAP) evoked by static contraction (DeltaMAP in mmHg: 38 +/- 10 before and 24 +/- 8 after ipsilateral Cap; 47 +/- 10 before and 33 +/- 10 after contralateral Cap). On the other hand, Cap increased the peak change in MAP evoked by stimulation of the saphenous nerve from 57 +/- 8 to 77 +/- 9 mmHg, as well as the peak change in MAP elicited by activation of muscle nociceptors (36 +/- 9 vs. 56 +/- 14 mmHg). These results show that the reflex cardiovascular increases evoked by static muscle contraction and noxious input are differentially affected by Cap application to the common peroneal nerve. We hypothesize that a Cap-induced alteration in dorsal horn processing is the locus for this divergent effect on these reflexes.