Reflex regulation of airway smooth muscle tone.

Autonomic nerves in most mammalian species mediate both contractions and relaxations of airway smooth muscle. Cholinergic-parasympathetic nerves mediate contractions, whereas adrenergic-sympathetic and/or noncholinergic parasympathetic nerves mediate relaxations. Sympathetic-adrenergic innervation of human airway smooth muscle is sparse or nonexistent based on histological analyses and plays little or no role in regulating airway caliber. Rather, in humans and in many other species, postganglionic noncholinergic parasympathetic nerves provide the only relaxant innervation of airway smooth muscle. These noncholinergic nerves are anatomically and physiologically distinct from the postganglionic cholinergic parasympathetic nerves and differentially regulated by reflexes. Although bronchopulmonary vagal afferent nerves provide the primary afferent input regulating airway autonomic nerve activity, extrapulmonary afferent nerves, both vagal and nonvagal, can also reflexively regulate autonomic tone in airway smooth muscle. Reflexes result in either an enhanced activity in one or more of the autonomic efferent pathways, or a withdrawal of baseline cholinergic tone. These parallel excitatory and inhibitory afferent and efferent pathways add complexity to autonomic control of airway caliber. Dysfunction or dysregulation of these afferent and efferent nerves likely contributes to the pathogenesis of obstructive airways diseases and may account for the pulmonary symptoms associated with extrapulmonary disorders, including gastroesophageal reflux disease, cardiovascular disease, and rhinosinusitis.     

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.     

Effects of high-frequency oscillatory ventilation on vagal and phrenic nerve activities

This study was undertaken to define the mechanism for the respiratory inhibition observed during high-frequency oscillatory ventilation (HFOV). The effects of HFOV on the activities of single units in the vagus (Vna) and phrenic nerves (Pna) were examined in pentobarbital-anesthetized dogs. The animals were either ventilated by intermittent positive-pressure ventilation (IPPV) with and without positive end-expiratory pressure (PEEP), or by HFOV at a frequency of 25 Hz and pump displacement volume of 3 ml/kg. In 13 vagal units the Vna was much higher during HFOV than during IPPV or airway occlusion at a matched airway pressure. Ten units in the phrenic nerves were examined, and Pna (expressed as bursts/min) was attenuated by HFOV in all of them. In four of them, the effect of cooling the vagi to 8-10 degrees C on Pna was examined, and it was found that HFOV failed to alter the Pna. We conclude that 1) HFOV stimulates the pulmonary vagal afferent fibers continuously and to a degree greater than that due to static lung inflation and increased airway pressure and 2) the increased vagal activity during HFOV probably causes phrenic nerve activity inhibition.     

The renal afferent nerves in the pathogenesis of hypertension

The renal nerves play a role in the pathogenesis of hypertension in a number of experimental models. In the deoxycorticosterone acetate - salt (DOCA-NaCl) hypertensive rat and the spontaneously hypertensive rat (SHR) of the Okamoto strain, total peripheral renal denervation delays the development and blunts the severity of hypertension and causes an increase in urinary sodium excretion, suggesting a renal efferent mechanism. Further, selective lesioning of the renal afferent nerves by dorsal rhizotomy reduces hypothalamic norepinephrine stores without altering the development of hypertension in the SHR, indicating that the renal afferent nerves do not play a major role in the development of hypertension in this genetic model. In contrast, the renal afferent nerves appear to be important in one-kidney, one-clip and two-kidney, one-clip Goldblatt hypertensive rats (1K, 1C and 2K, 1C, respectively) and in dogs with chronic coarctation hypertension. Total peripheral renal denervation attenuates the severity of hypertension in these models, mainly by interrupting renal afferent nerve activity, which by a direct feedback mechanism attenuates systemic sympathetic tone, thereby lowering blood pressure. Peripheral renal denervation has a peripheral sympatholytic effect and alters the level of activation of central noradrenergic pathways but does not alter sodium or water intake or excretion, plasma renin activity or creatinine clearance, suggesting that efferent renal nerve function does not play an important role in the maintenance of this form of hypertension. Selective lesioning of the renal afferent nerves attenuates the development of hypertension, thus giving direct evidence that the renal afferent nerves participate in the pathogenesis of renovascular hypertension.     

Innervation of the renal vasculature of the toad (Bufo marinus)

The innervation of the dorsal aorta and renal vasculature in the toad (Bufo marinus) has been studied with both fluorescence and ultrastructural histochemistry. The innervation consists primarily of a dense plexus of adrenergic nerves associated with all levels of the preglomerular vasculature. Non-adrenergic nerves are occasionally found in the renal artery, and even more rarely near the afferent arterioles. Many of the adrenergic nerve profiles in the dorsal aorta and renal vasculature are distinguished by high proportions of chromaffin-negative, large, filled vesicles. Close neuromuscular contacts are common in both the renal arteries and afferent arterioles. Possibly every smooth muscle cell in the afferent arterioles is multiply innervated. The glomerular capillaries and peritubular vessels are not innervated, and only 3-5% of efferent arterioles are accompanied by single adrenergic nerve fibres. Thus, nervous control of glomerular blood flow must be exerted primarily by adrenergic nerves acting on the preglomerular vasculature. The adrenergic innervation of the renal portal veins and efferent renal veins may play a role in regulating peritubular blood flow. In addition, glomerular and postglomerular control of renal blood flow could be achieved by circulating agents acting via contractile elements in the glomerular mesangial cells, and in the endothelial cells and pericytes of the efferent arterioles. Some adrenergic nerve profiles near afferent arterioles are as close as 70 nm to distal tubule cells, indicating that tubular function may be directly controlled by adrenergic nerves.     

Selective stimulation of jugular ganglion afferent neurons in guinea pig airways by hypertonic saline

Pedersen, Karen E., Sonya N. Meeker, Margerita M. Riccio,and Bradley J. Undem. Selective stimulation ofjugular ganglion afferent neurons in guinea pig airways by hypertonicsaline. J. Appl. Physiol. 84(2):499-506, 1998.We evaluated the ability of hyperosmolar stimulito activate afferent nerves in the guinea pig trachea and main bronchiand investigated the neural pathways involved. By usingelectrophysiological techniques, studies in vitro examined the effectof hyperosmolar solutions of sodium chloride (hypertonic saline) onguinea pig airway afferent nerve endings arising from either vagalnodose or jugular ganglia. The data reveal a differential sensitivityof airway afferent neurons to activation with hypertonic saline.Afferent fibers (both A and C fibers) with cell bodies located injugular ganglia were much more sensitive to stimulation with hypertonicsaline, compared with afferent neurons with cell bodies located innodose ganglia. Additional studies in vivo demonstrated that inhalationof aerosols of hypertonic saline induced plasma extravasation in guineapig trachea that was mediated via tachykininNK₁ receptors. Identification of adifferential sensitivity of guinea pig airway afferent nerves tohypertonic saline leads to the speculation that airway responses tohyperosmolar stimuli may result from activation of afferent neuronsoriginating predominantly from the jugular ganglion.

     

Differential effects of airway afferent nerve subtypes on cough and respiration in anesthetized guinea pigs

The hypothesis that respiratory reflexes, such as cough, reflect the net and often opposing effects of activation of multiple afferent nerve subpopulations throughout the airways was evaluated. Laryngeal and tracheal mucosal challenge with either citric acid or mechanical probing reliably evoked coughing in anesthetized guinea pigs. No other stimulus reliably evoked coughing in these animals, regardless of route of administration and despite some profound effects on respiration. Selectively activating vagal C-fibers arising from the nodose ganglia with either adenosine or 2-methyl-5-HT evoked only tachypnea. Selectively activating vagal afferents arising from the jugular ganglia induced respiratory slowing and apnea. Nasal afferent nerve activation by capsaicin, citric acid, hypertonic saline, or histamine evoked only respiratory slowing. Histamine, which activates intrapulmonary rapidly adapting receptors but not airway or lung C-fibers or tracheal bronchial cough receptors induced bronchospasm and tachypnea, but no coughing. The results indicate that the reflexes initiated by stimuli thought to be selective for some afferent nerve subtypes will likely depend on the net and potentially opposing effects of multiple afferent nerve subpopulations throughout the airways. The data also provide further evidence that the afferent nerves regulating cough in anesthetized guinea pigs are distinct from either C-fibers or intrapulmonary rapidly adapting receptors.     

Sensory receptors on the hindgut of the cockroach, Leucophaea maderae Fabricius (Dictyoptera: Blaberidae)

In the cockroach, Leucophaea maderae, the hindgut is innervated by the proctodeal nerves, branches of nerves XI of the terminal abdominal ganglion.Phasic afferent activity was recorded from the 11th-proctodeal nerve in response to distention of the hindgut by saline injection. With methylene blue staining, eight multipolar sensory receptors of type II (Dethier, 1963, The Physiology of Insect Senses. Methuen, London) were identified on the ventral and lateral surfaces of the rectum, four on each side. The afferent activity in the 11th-proctodeal nerve most likely originated in these receptors.     

家兔主动脉神经低阈压力感受反射快速重调中枢过程的特征

40只家兔,乌拉坦静脉麻醉。切断双侧主动脉神经(AN)、窦神经及迷走神经。以选择兴奋 AN 有髓传人纤维的条件刺激(0.02ms,50Hz,4—6V,5min)给予切断的 AN 中枢段,模拟导致低阈压力感受反射快速重调的保持压背景,借以诱导快速重调的中枢过程。实验表明:该中枢过程使 AN 有髓纤维传入所激发的压力感受反射降压效应衰减41.82%(P<0.01),肾交感神经活动抑制效应衰减19.31%(P相似文献   

Homeostasis in the gastric mucosa and blood circulation. Part 1. Mechanisms of the adequate blood flow maintenance in the gastric mucosa]

The increase of mucosal blood flow in response to food entrance into stomach or different irritant action is the component of gastric mucosal defence barrier. Sufficient blood flow ensures normal acid-bicarbonate balance in gastric mucosa, supports the healing process and prevents superficial damages from developing into deep ones. Capsaicin-sensitive afferent nerve fibers play the large role in the blood flow regulation. The influence of these nerve fibers on the gastric blood flow is mediated by the calcitonin-gene related peptide. This peptide released from peripheral afferent terminals improves microcirculation in stomach walls. Moreover nerve impulses from afferent neurons modulate parasympathetic activity that in turn induces the increase of gastric mucosal blood flow through both choilinergic and noncholinergic mechanisms. The gastric mucosal blood flow may be also regulated by humoral and paracrine metabolites. Nitric oxide and prostaglandines are the most important low molecular weight compounds. They play the main role in the maintenance of the basal gastric mucosal blood flow and in the development of hyperemic responses to harmful agents.     

Biopotential amplifier with nonlinear volt-ampere characteristics for recording low-amplitude pulses

An amplifier with non-linear volt-ampere characteristics for recording low-amplitude nerve pulse activity is offered. It permits recording impulses with an amplitude exceeding the noise by 3-5 microV and afferent impulse activity of rat taste nerves.     

Transient contractions of urinary bladder smooth muscle are drivers of afferent nerve activity during filling

Activation of afferent nerves during urinary bladder (UB) filling conveys the sensation of UB fullness to the central nervous system (CNS). Although this sensory outflow is presumed to reflect graded increases in pressure associated with filling, UBs also exhibit nonvoiding, transient contractions (TCs) that cause small, rapid increases in intravesical pressure. Here, using an ex vivo mouse bladder preparation, we explored the relative contributions of filling pressure and TC-induced pressure transients to sensory nerve stimulation. Continuous UB filling caused an increase in afferent nerve activity composed of a graded increase in baseline activity and activity associated with increases in intravesical pressure produced by TCs. For each ∼4-mmHg pressure increase, filling pressure increased baseline afferent activity by ∼60 action potentials per second. In contrast, a similar pressure elevation induced by a TC evoked an ∼10-fold greater increase in afferent activity. Filling pressure did not affect TC frequency but did increase the TC rate of rise, reflecting a change in the length-tension relationship of detrusor smooth muscle. The frequency of afferent bursts depended on the TC rate of rise and peaked before maximum pressure. Inhibition of small- and large-conductance Ca²⁺-activated K⁺ (SK and BK) channels increased TC amplitude and afferent nerve activity. After inhibiting detrusor muscle contractility, simulating the waveform of a TC by gently compressing the bladder evoked similar increases in afferent activity. Notably, afferent activity elicited by simulated TCs was augmented by SK channel inhibition. Our results show that afferent nerve activity evoked by TCs represents the majority of afferent outflow conveyed to the CNS during UB filling and suggest that the maximum TC rate of rise corresponds to an optimal length-tension relationship for efficient UB contraction. Furthermore, our findings implicate SK channels in controlling the gain of sensory outflow independent of UB contractility.     

Central representation and functional connections of afferent and efferent pathways of Helix pomatia L. lip nerves

Localization and distribution of cerebral neurones sending axons into the three pairs of Helix pomatia lip nerves were investigated by the method of retrograde axonal NiCl2 transport. Using electrophysiological technics (extracellular recordings) the dependence of lip nerve's activity on inputs of other lip nerves was studied after application of various types of stimuli to the lip of semi-intact preparations. All lip nerves have neuronal representation in each lobe of the cerebral ganglia but in different proportions. Labelled neurones were located mainly on the ventral surface of the cerebral ganglia, most of them projecting to the medial, the least to the inner lip nerve. Lip nerves differ from each other according to the proportions of neurones of various size. They share in the axons of large (55-70 microns) and medium sized (30-40 microns) neurones in the order inner greater than outer greater than medial and medial greater than outer greater than inner lip nerve, respectively. Most neurones projecting to different nerves are located in discrete groups. According to the electrophysiological results the medial lip nerve has the most prominent afferent, while the inner one has the strongest efferent activity. Both the afferent and efferent activities of the outer lip nerve proved to be the least significant compared to the other lip nerves. Contralateral cerebral connections play an important role in the sensory information processing. The sensory input of a given nerve usually activates the contralateral member of another pair of lip nerves. Mechano- and chemo-afferent pathways have almost the same properties but there are some differences in latencies and other parameters.     

Organization of reflex sympathetic influence on rate and force of cardiac contraction]

In acute experiments on 21 cats it was proved that the change of afferent impulse on vagus nerves by means of either freeze-block or electrostimulation of their central ends results in differential reflex influences on rhythm and force of the cardiac contractions caused by sympathetic nervous system. The cut of the lower cardiac nerves may cause 'break-up' of the observed reflex, removing or inverting its ino- or chronotropy component. The given phenomenon was revealed in the experiments with high arterial pressure and with absence of tonic chronotropy influences of the left lower cardiac nerve.     

Neuronal control of the kidney: contribution to hypertension.

The renal nerves contribute to hypertension in experimental models of the disease, and appear to play a role in human hypertension. Several lines of evidence indicate that both in spontaneously hypertensive rats and in deoxycorticosterone acetate--NaCl rats, the full development of hypertension is dependent on renal efferent nerves and their induction of excess sodium retention. Renal sensory (afferent nerve) feedback to the central nervous system does not contribute to either of these forms of hypertension. In contrast, renovascular hypertension in rats and aortic coarctation hypertension in dogs are mediated, at least in part, by overactivity of renal afferent nerves and a resultant increase in systemic sympathetic nervous system activity. These forms of hypertension are not associated with sodium retention, and selective sensory denervation of renal afferent nerves by dorsal rhizotomy and total renal denervation result in similar reductions in hypertension. Surprisingly, the renal nerves do not contribute to dietary NaCl exacerbated hypertension in the spontaneously hypertensive rat, dietary NaCl-induced hypertension in the Dahl NaCl-sensitive rat, or the chronic hypertensive and nephrotoxic effects of cyclosporine A therapy in the rat, despite the finding that in all three forms of hypertension, overactivity of the sympathetic nervous system is prominent. Clinical studies indicate that the renal afferent and efferent nerves contribute to hypertension of different etiologies. Together these data point to the complex role that the renal nerves likely play in human essential hypertension.     

Biocybernetic studies on reflectory heart modification in the rabbit]

In rabbits the depressor nerves and cardiac vagal branches were stimulated. Their actions on heart rate, atrio-ventricular conduction time, myocardial action potential and mean central blood pressure were recorded. The frequency-effect characteristics of the chronotropic, dromotropic and electrotropic actions on the heart, resulting from afferent and efferent nerve stimulation, are compared. The participation of each of the depressor nerves in their total effects on heart rate and blood pressure is studied. Time courses of heart rate and blood pressure decrease by afferent and efferent nerve stimulation with sinusoidally modulated pulse rates are presented. The results are discussed with respect to the different dynamics of blood pressure and heart rate control. It is concluded that at least two mechanisms are involved in blood pressure control by the depressor nerves: 1. Decrease of vascular resistance by lowering the sympathetic tone. 2. Decrease of heart rate by enhancing the cardiac vagal activity. It is suggested that the parasympathetic control unit compensates rapid disturbances, whereas the slow-acting sympathetic vascular mechanism exerts a long-time pressure control of high efficiency.     

CGRP immunoreactivity and NADPH-diaphorase in afferent nerves of the rat penis

Calcitonin gene-related peptide (CGRP)-immunoreactive afferent nerve fibers are abundant in the rat penis. In addition, NADPH-diaphorase, which stains for nitric oxide synthase, has been localized within both autonomic and sensory dorsal root ganglia (DRG) and may be part of an important biochemical pathway involved in penile tumescence. The purpose of this study was: 1) to examine the circuitry of afferent nerves that are CGRP immunoreactive from the L6 DRG, 2) to examine the possibility that there are NADPH-diaphorase-positive afferent fibers from the L6 DRG to the rat penis, and 3) to examine the localization and colocalization of CGRP and NADPH-diaphorase within L6 DRG afferent perikarya. Calcitonin gene-related peptide immunostaining in the penis was eliminated following a bilateral transection of the pudendal nerves, but was unchanged following a bilateral transection of the pelvic splanchnic or hypogastric nerves. The NADPH-diaphorase staining was not altered by any of the nerve transections. Injection of the retrograde axonal tracer fluorogold (FG) into the dorsum penis labeled perikarya in the L6 DRG. Although the majority of FG-labeled perikarya contained neither CGRP nor NADPH-diaphorase, small subpopulations of perikarya contained either CGRP immunoreactivity, NADPH-diaphorase, or both. A unilateral pudendal nerve transection virtually eliminated (>99%) FG labeling in the ipsilateral L6 DRG. These data suggest that NADPH-diaphorase and CGRP are present, either together or separately, within a subpopulation of penile afferent perikarya. In addition, CGRP-immunoreactive afferent nerve fibers reach the penis primarily via the pudendal nerves. Finally, NADPH-diaphorase-positive penile afferents may be another important source of nitric oxide (NO) for penile tumescence.     

Preliminary results on the splanchnico-laryngeal reflex in the cat]

Electrical stimulation of low threshold splanchnic afferent nerves in lightly anesthetized cat results in phrenic and recurrent laryngeal nerve responses. Both phrenic and recurrent laryngeal inspiratory nerve activities are inhibited, whereas expiratory recurrent nerve activity is triggered and even increased. The significance of this reflex is discussed in relation to laryngeal adductor muscle contractions and the abdominal pressure increase.     

Afferent and efferent components of the facial nerve in the bullfrog (Rana catesbeiana).

The afferent and efferent components of the facial nerve were traced within the brain stem of Rana catesbeiana, using three different neuroanatomical techniques. Primary afferent fibers could be traced to the spinal tract of trigeminal nerve and to fasciculus solitarius as far caudally as the first or second spinal segment, using silver degeneration methods. Cobalt filling of of the entire nerve showed the same distribution of afferent fibers, as well as the filling of the cells within the mesencephalic nucleus of trigeminal, indicating the origin of a proprioceptive component of the facial nerve. Cobalt iontophoresis and horseradish perioxidase experiments showed that the motor nucleus of the facial nerve was located just ventral to the fourth ventricle, and caudal to the motor nucleus of trigeminal. The distribution of afferent fibers to fasciculus solitarius and the spinal tract of trigeminal is similar in some respects to the distribution of afferent fibers from the trigeminal and vagal nerves in the bullfrog. The afferent fibers from the three cranial nerves are found as far caudally in the brain stem as the second spinal segment.     

Renal nerves and hypertension: an update

Increased efferent renal sympathetic nerve activity could facilitate the development of hypertension by shifting the arterial pressure-renal sodium excretion curve to the right. Accordingly, interruption of the renal nerves should prevent the development of hypertension in animal models in which increased sympathetic nervous system activity has been implicated. Renal denervation delays the development of hypertension and results in greater sodium excretion in the Okamoto and New Zealand spontaneously hypertensive rat and in the deoxycorticosterone acetate-salt-treated rat, which suggests that these responses result from, at least in part, loss of efferent renal nerve activity. Similar sympathetically mediated renal vasoconstriction has been implicated in the pathogenesis of early essential hypertension in humans. The efferent renal sympathetic nerves play a diminishing role once hypertension is established in these models. Renal denervation in established one-kidney, one-clip and two-kidney, one-clip Goldblatt hypertension in the rat and chronic coarctation in the dog results in an attenuation of the hypertension. The depressor effect of renal denervation in these models is not caused by changes in renin activity or sodium excretion but is associated with decreased sympathoadrenal activity. These findings suggest that the afferent renal nerves contribute to the pathogenesis of renovascular hypertension by enhancing the activity of the sympathetic nervous system. Interruption of afferent renal fibers also appears to be the mechanism by which renal denervation prevents or reverses the normal increase in arterial pressure seen after aortic baroreceptor deafferentation in the rat.