Disruption of primary and secondary esophageal peristalsis by afferent stimulation

Recent studies have shown that afferent signals originating from the pharynx inhibit progression of primary esophageal peristalsis. Our aim was to further elucidate the effect of esophageal and pharyngeal afferent stimulation on primary and secondary esophageal peristalsis. We studied the effect of esophageal air distension and pharyngeal water stimulation on progression of primary and secondary peristalsis in nine healthy volunteers aged 27 +/- 2 yr (4 men, 5 women). At a threshold volume, rapid injection of water into the pharynx, directed posteriorly, resulted in complete halt of the progressing secondary and primary esophageal peristalses in both the proximal and distal esophagus. The threshold volume of injected water for inducing inhibition was similar for secondary (0.6 +/- 0.2 ml) and primary (0.5 +/- 0.1 ml) esophageal peristalsis. Progression of primary peristalsis induced by a dry swallow and secondary peristalsis induced by intraesophageal air distension were completely inhibited by intraesophageal injection of 15 +/- 2 ml of air in 70% and 75% of the trials, respectively. We conclude that afferent signals induced by esophageal air distension and pharyngeal water stimulation inhibit propagation of both primary and secondary esophageal peristalsis, suggesting a shared neural control mechanism for these types of peristalsis.     

Capsaicin-sensitive vagal fibres and 5-HT3-, gastrin releasing peptide- and cholecystokinin A-receptors are involved in distension-induced inhibition of gastric emptying in the rat.

The present study was undertaken to investigate how the activation of gastric mechanoreceptors by distension of the stomach in conscious gastric fistula rats influences gastric emptying; and the roles of capsaicin sensitive vagal afferent fibres and the 5-HT3, GRP and CCK-A receptors involved in mediating these responses. To activate mechanoreceptors by non-nutrient dependent pathways, methylcellulose in saline was used to distend the stomach (5 cm H2O) and the subsequent emptying of saline was examined immediately, and at 3, 5 and 10 min following distension. Prior distension delayed the subsequent emptying of saline instilled into the stomach compared with non-distended controls (2.28+/-0.09 ml/5 min; P < 0.001). Topical application of capsaicin, completely abolished the distension-induced inhibition of gastric emptying when compared with vehicle treated rats (2.82+/-0.09 vs. 2.38+/-0.04 ml/5 min; P < 0.001). Peripheral administration of a GRP antagonist (2258 U89UJ, 1 mg/kg), and a 5-HT3 antagonist (BRL4369UA, 50 microg/kg) significantly reversed (2.56+/-0.14 ml/5 min; P < 0.05 and 2.61+/-0.07 ml/5 min; P < 0.01; respectively) the delay in gastric emptying induced by distension. When the rats were treated with the CCK-A antagonist, gastric emptying of saline following distension was also significantly facilitated (2.56+/-0.07 ml/5 min; P < 0.001). In contrast, the CCK-B/gastrin receptor antagonist had no significant effect on the distension induced delay in gastric emptying (1.95+/-0.12 ml/5 min). The present results suggest that gastric distension in conscious gastric fistula rats delays gastric emptying by activating capsaicin-sensitive extrinsic afferent nerve fibres. Moreover, the results also indicate that distension-induced mechanisms involve GRP, 5-HT3 and CCK-A receptors, but not CCK-B receptors.     

Parametric analysis of gastric distension responses in the parabrachial nucleus

The parabrachial nucleus (PBN) is regarded as an important locus for the processing and integration of sensory inputs from oral, gastrointestinal, and postabsorptive receptor sites and is thus thought to play an important role in regulating food intake. Gastric distension is an important satiation cue; however, such responses have been qualitatively characterized only over a limited area of the PBN. To more fully characterize gastric distension responses throughout the PBN, the responses of single units to gastric distension were tested using computer-controlled balloon inflation (3-18 ml air) in pentobarbital sodium- and/or urethan-anesthetized male rats. Distension-responsive neurons were indeed distributed throughout the nucleus from rostral areas typically considered to be visceral to more caudal areas associated with gustatory function, providing further anatomical support for the hypothesis that the PBN integrates taste and visceral signals that control feeding. Most PBN neurons had thresholds of 6 ml or less, similar to vagal afferent fibers. However, in contrast to the periphery, there were both excitatory and inhibitory responses. Increases in volume were associated with two distinct effects. First, as volume increased, the response rate increased; second, the duration of the response increased. In fact, in a subset of cells, responses to gastric distension lasted well beyond the stimulation period, particularly at larger volumes. Prolonged gastric distension responses are not common in the periphery and may constitute a central mechanism that contributes to satiation processes.     

Modulation of gastric distension-induced sensations by small intestinal receptors

Duodenal lipid exacerbates gastrointestinal sensations during gastric distension. Using luminal application of the local anesthetic benzocaine, we investigated the role of intestinal receptors in the induction of these sensations. Nine healthy subjects were studied on five occasions, during which isotonic saline or 20% lipid (2 kcal/min), combined with (duodenal or jejunal) 0.75% benzocaine or vehicle at 2.5 ml/min, was infused intraduodenally before and during gastric distension. Intragastric pressures and volumes, gastrointestinal sensations, and plasma CCK levels were determined. Duodenal lipid combined with vehicle increased gastric volume (in ml: saline, -10 +/- 18; lipid/vehicle, 237 +/- 30) and plasma CCK [mean levels (pmol/l): saline, 2.0 +/- 0. 2; lipid/vehicle, 8.0 +/- 1.6] and, during distensions, induced nausea (scores: saline, 3 +/- 2: lipid/vehicle, 58 +/- 19) and decreased pressures at which fullness and discomfort occurred. Duodenal but not jejunal benzocaine attenuated the effect of lipid on gastric volume, plasma CCK, and nausea during distension (135 +/- 38 and 216 +/- 40 ml, 4.6 +/- 0.6 pmol/l and not assessed, and 37 +/- 12 and 64 +/- 21 for lipid + duodenal benzocaine and lipid + jejunal benzocaine, respectively) and on pressures for sensations. In conclusion, intestinal receptors modulate gastrointestinal sensations associated with duodenal lipid and gastric distension. There is also the potential for local neural mechanisms to regulate CCK release and thereby reduce afferent activation indirectly.     

Characteristics of distension-induced release of immunoreactive atrial natriuretic peptide in isolated perfused rabbit atria

Atrial pressure- or distension-induced release of atrial natriuretic peptide (ANP) has been considered as an important regulatory mechanism of ANP release in cardiac atria. A new technique to permit graded continuous atrial distension has been developed in an isolated perfused single rabbit atrium. Graded atrial distension was induced by changing the elevation of the outflow catheter tip. Intra-atrial volume expansion resulted in an increase in immunoreactive ANP release. The graded increase in atrial distension from 43.9 +/- 10.2 to 207.7 +/- 29.1 microliter resulted in 6.2-27.1-fold increases in volume-dependent immunoreactive ANP release. A rise in immunoreactive ANP release induced by increasing atrial distension did not occur in the state of atrial distension but occurred only after return to the reduced distension. However, in the case of atrial distension with pacing, an increase in immunoreactive ANP release was observed during atrial distension with pacing and after return to the basal level. The present study shows that the new technique is applicable to the study of the 'stretch-secretion coupling' mechanism of ANP release in vitro, and that the more important factor involved in the release of immunoreactive ANP induced by atrial distension may be the atrial reduction to basal level after distension rather than the stretch itself.     

Modulatory influences on antegrade and retrograde tonic reflexes in the colon and rectum

Tonic reflexes in the colon and rectum are likely to be important in health and in disorders of gastrointestinal function. The aim of this study was to evaluate the fasting and postprandial "colorectal" and "rectocolic" reflexes in response to 2-min isobaric distensions of the colon and rectum, accounting for enteric sensation, compliance, and distending balloon volume. In 14 healthy fasting subjects, a dual barostat assembly was positioned (descending colon and rectum). A 2-min phasic distension was performed in the colon and rectum in random order while the opposing balloon volume was recorded. Sensation (phasic distension) and compliance (ramp distension) were also determined. The experiment was repeated postprandially. Colonic distension resulted in significant rectal tonic contraction in the fasting (rectal volume change: -35.4 +/- 8.4 ml, P < 0.01) and postprandial (-22.2 +/- 8.4 ml, P < 0.01) states. After adjustment for colonic sensitivity, for compliance, and for distending balloon volume, the rectal volume change remained significant; the extent of the tonic response, however, correlated significantly with increasing pain score (P < 0.01). In contrast, rectal distension did not produce a significant tonic response in the colon (fasting: -6.5 +/- 7.3 ml; postprandial: 2.7 +/- 7.3 ml), either unadjusted or adjusted for rectal sensitivity, compliance, and distending balloon volume. In conclusion, the colorectal reflex, but not the rectocolic reflex, can be readily demonstrated both before and after a meal in response to a 2-min isobaric distension in the colon and rectum, respectively. Although the presence of the colorectal reflex does not depend on colonic sensitivity or the volume of the distending colonic balloon, these factors modulate the reflex, especially in the fasting state.     

Preferential axial flow during high-frequency oscillations: effects of gas density

Allen et al. (J. Clin. Invest. 76: 620-629, 1985) reported that regional phasic lung distension during high-frequency oscillations (HFO) is substantially and systemically heterogeneous when both frequency (f) and tidal volume (VT) are large. They hypothesized that this phenomenon was attributable to central airway geometry and preferential axial flow induced therein by the momentum flux of the inspiratory gas stream. According to that hypothesis, the observed distribution of phasic lung distension would depend on the ratio VT/VD* (where VD* is an index of anatomic dead space), independent of gas density (rho), when f is scaled in proportion to lung resonant frequency, fo. To test this hypothesis, we used the methods of Allen et al. (ibid.) to study six excised dog lungs during HFO (f = 2-32 Hz; VT = 5-80 ml) using gases of different densities. Alveolar pressure excursions (PA) were measured as rho spanned a 12-fold range using He, air, and SF6. The apex-to-base and right-to-left ratios of PA were used as indexes of regional heterogeneity of phasic lung distension. For each gas at low f, distension of the lung base was favored slightly independent of VT, but at higher f distension of the lung apex was favored when VT was small, whereas distension of the lung base was favored when VT was large. In addition, we observed substantial right-to-left differences in apical lobes during oscillation at high f not seen before.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cholecystokinin and stomach distension combine to reduce food intake in humans

The aim of this study was to test the hypothesis that gastric distension can enhance the effect of cholecystokinin (CCK) on reduction of food intake in men and women. Eight normal-weight subjects of each gender were tested four times each with either CCK or saline infusion crossed with gastric distension or no distension. Intravenous infusion of a low dose of CCK octapeptide (CCK-8; 112 ng/min for 23 min) combined with a subthreshold gastric distension induced by a water-filled balloon (300 ml) resulted in a significant (means +/- SED: 191 +/- 61 g in men, 209 +/- 61 g in women, and 200 +/- 43 g combined) reduction in intake of a liquid meal compared with saline infusion and unfilled gastric balloon. This combined effect was the result of a large and significant CCK effect when the stomach was distended (CCK vs. saline with distension: 169 +/- 43 g) and a small and insignificant distension effect (distension vs. no distension without CCK: 31 +/- 43 g). The CCK effect alone on intake (CCK vs. saline) without distension was not significant in men (72 +/- 61 g) but was significant in women (121 +/- 61 g). These results are consistent with the hypothesis that CCK's suppression of food intake is enhanced when the stomach is distended.     

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.     

Effects of variations in intragastric volume on blood pressure and splanchnic blood flow during intraduodenal glucose infusion in healthy older subjects

The postprandial reduction in blood pressure (BP) is triggered by the interaction of nutrients with the small intestine and associated with an increase in splanchnic blood flow. Gastric distension may attenuate the postprandial fall in BP. The aim of this study was to determine the effects of differences in intragastric volume, including distension at a low (100 ml) volume, on BP and superior mesenteric artery (SMA) blood flow responses to intraduodenal glucose in healthy older subjects. BP and heart rate (HR; automated device), SMA blood flow (Doppler ultrasound), mesenteric vascular resistance (MVR), and plasma norepinephrine of nine male subjects (65-75 yr old) were measured after an overnight fast on 4 separate days in random order. On each day, subjects were intubated with a nasoduodenal catheter, incorporating a duodenal infusion port, and orally with a second catheter, incorporating a barostat bag, positioned in the fundus. Each subject received a 60-min (t = 0-60 min) intraduodenal glucose infusion (3 kcal/min) and gastric distension at a volume of 1) 0 ml (V0), 2) 100 ml (V100), 3) 300 ml (V300), or 4) 500 ml (V500). Systolic BP fell (P < 0.05) during V0, but not during V100, V300, or V500. In contrast, HR (P < 0.01) and SMA blood flow (P < 0.001) increased and MVR decreased (P < 0.05) comparably on all 4 days. Plasma norepinephrine rose (P < 0.01) in response to intraduodenal glucose, with no difference between the four treatments. There was a relationship between the areas under the curve for the change in systolic BP from baseline with intragastric volume (r = 0.60, P < 0.001). In conclusion, low-volume (≤100 ml) gastric distension has the capacity to abolish the fall in BP induced by intraduodenal glucose in healthy older subjects without affecting SMA blood flow or MVR. These observations support the concept that nonnutrient gastric distension prior to a meal has potential therapeutic applications in the management of postprandial hypotension.     

Attenuation of the colorectal tonic reflex in female patients with irritable bowel syndrome

Alterations in normal intestinointestinal reflexes may be important contributors to the pathophysiology of irritable bowel syndrome (IBS). Our aims were to compare the rectal tonic responses to colonic distension in female IBS patients with predominant constipation (IBS-C) and with predominant diarrhea (IBS-D) to those in healthy females, both fasting and postprandially. Using a dual barostat assembly, 2-min colonic phasic distensions were performed during fasting and postprandially. Rectal tone was recorded before, during, and after the phasic distension. Colonic compliance and colonic sensitivity in response to the distension were also evaluated fasting and postprandially. Eight IBS-C patients, 8 IBS-D patients, and 8 age- and sex-matched healthy subjects (group N) participated. The fasting increments in rectal tone in response to colonic distension in both IBS-C (rectal balloon volume change -4.6 +/- 6.1 ml) and IBS-D (-7.9 +/- 4.9 ml) were significantly reduced compared with group N (-34 +/- 9.7 ml, P = 0.01). Similar findings were observed postprandially (P = 0.02). When adjusted for the colonic compliance of individual subjects, the degree of attenuation in the rectal tonic response in IBS compared with group N was maintained (fasting P = 0.007; postprandial P = 0.03). When adjusted for colonic sensitivity there was a trend for the attenuation in the rectal tonic response in IBS patients compared with group N to be maintained (fasting P = 0.07, postprandial P = 0.08). IBS patients display a definite attenuation of the normal increase in rectal tone in response to colonic distension (colorectal reflex), fasting and postprandially. Alterations in colonic compliance and sensitivity in IBS are not likely to contribute to such attenuation.     

Enhancement of antral contractions and vagal afferent signaling with synchronized electrical stimulation

Gastric filling activates vagal afferents involved in peripheral signaling to the central nervous system (CNS) for food intake. It is not known whether these afferents linearly encode increasing contractions of the antrum during antral distension (AD). The aim of this study was to investigate effects of AD and electrically enhanced antral contractions on responses of vagal afferents innervating the antrum. Single-fiber recordings were made from the vagal afferents in anesthetized male Long-Evans rats. Antral contractions were measured with a solid-state probe placed in the antrum. A nonexcitatory electrical stimulation (NES) inducing no smooth muscle contractions was applied during the ascending phase of antral contractions to enhance subsequent antral contractions. Fifty-six fibers identified during AD (1 ml for 30 s) were studied through different types of mechanical stimuli. Under normal conditions, one group of fibers exhibited rhythmic firing in phase with antral contractions. Another group of fibers had nonrhythmic spontaneous firing. Responses of 15 fibers were tested with NES during multiple-step distension (MSD). NES produced a mean increase in antral contraction amplitude (177.1 +/- 35.3%) and vagal afferent firing (21.6 +/- 2.6%). Results show that both passive distension and enhanced antral contractions activate distension-sensitive vagal afferents. Responses of these fibers increase linearly to enhanced antral contraction induced by NES or MSD up to a distending volume of 0.6 ml. However, responses reached a plateau at a distending volume >0.8 ml. We concluded that enhanced contraction of the antrum can activate vagal afferents signaling to the CNS.     

Intraluminal modulation of gastric sensitivity to distension: effects of hydrochloric acid and meal

Conscious sensations in response to gut distensions may be modulated by temporospatial interactions among different stimuli. This study investigated whether symptoms induced by gastric distension may be modified by hydrochloric acid (HCl) gastric infusion and meal ingestion. In nine healthy subjects, fixed pressure (isobaric) and fixed volume (isovolumetric) distensions were performed during continuous (4 ml/min) intragastric saline or HCl infusion, during fasting and after meal ingestion, until the maximal distension step defined as discomfort or a predefined maximal volume. During fasting isobaric distensions, the maximal distension step was significantly decreased during HCl compared with saline. The intragastric volumes were not significantly different, but the wall tension was significantly lower during HCl than saline. HCl increased gastric compliance. Meal ingestion relaxed the stomach and decreased the pressure at the maximal distension step during saline, but HCl did not further decrease it compared with fasting. During isovolumetric distensions, HCl also increased gastric compliance, but in both fasted and fed states it did not modify the maximal distension steps. In conclusion, sensations in response to gastric isobaric distensions, but not to isovolumetric distensions, are influenced by gastric acid infusion and meal ingestion. The effects of HCl might be related to a sensitization of mucosal mechanoreceptors.     

Induction of body distension by operations on the nervous system in larvae of the swallowtall, Papilio xuthus

Removal of the ganglion or severance of the nerve cords at the thorax in mature larvae of the swallowtail, Papilio xuthus, induced systemic distension of the body by swallowing excess air. Such a distension, however, was never induced by simultaneous extirpation of the brain, suboesophageal ganglion, or frontal ganglion, or by severance of the recurrent nerve. Removal of an abdominal ganglion induced distension of the posterior part of the body accompanied by shrinkage of the anterior part. The latter phenomenon appears to be induced by a different mechanism from that of systemic distension.     

Pressure-distension relationship in arteries and arterioles in response to 5 wk of horizontal bedrest

We hypothesized that exposure to prolonged recumbency (bedrest), and thus reductions of intravascular pressure gradients, increases pressure distension in arteries/arterioles in the legs. Ten subjects underwent 5 wk of horizontal bedrest. Pressure distension was investigated in arteries and arterioles before and after the bedrest, with the subject seated or supine in a hyperbaric chamber with either one arm or a lower leg protruding through a hole in the chamber door. Increased pressure in the vessels of the arm/leg was accomplished by increasing chamber pressure. Vessel diameter and flow were measured in the brachial and posterior tibial arteries using Doppler ultrasonography. Electrical tissue impedance was measured in the test limb. Bedrest increased (P < 0.01) pressure distension threefold in the tibial artery (from 8 +/- 7% to 24 +/- 11%) and by a third (P < 0.05) in the brachial artery (from 15 +/- 9% to 20 +/- 10%). The pressure-induced increase in tibial artery flow was more pronounced (P < 0.01) after (50 +/- 39 ml/min) than before (13 +/- 23 ml/min) bedrest, whereas the brachial artery flow response was unaffected by bedrest. The pressure-induced decrease in tissue impedance in the leg was more pronounced (P < 0.01) after (16 +/- 7%) than before (10 +/- 6%) bedrest, whereas bedrest did not affect the impedance response in the arm. Thus, withdrawal of the hydrostatic pressure gradients that act along the blood vessels in erect posture markedly increases pressure distension in dependent arteries and arterioles.     

Visceral pain decreases tolerance to blood loss in conscious female but not male rabbits

Pain is a component of traumatic blood loss, yet little is known about how pain alters the response to blood loss in conscious animals. We evaluated the effects of colorectal distension on the cardiorespiratory response to blood loss in six male and six female conscious, chronically instrumented New Zealand White rabbits. The goal of these experiments was to test the hypotheses that 1) colorectal distension would increase tolerance to hemorrhage (i.e., increase the blood loss required to decrease mean arterial pressure 相似文献   

Interdependency of stress relaxation and afferent nerve discharge in rat small intestine

Background and aimsTo be able to characterize intestinal mechano-electrical transduction, i.e. the mechanoreceptor behaviour, quantitative nerve studies with controlled and quantified stimulus are needed. This study aimed to determine the relationship between mechanical stress relaxation and afferent discharge adaptation evoked by fast isovolumetric bag distensions in the rat jejunum.MethodsMultiunit afferent activity was recorded in vivo from jejunum afferents from five male Wistar rats. The jejunum was distended via a bag at a distension speed of 0.5 ml/s to volumes of 0.2, 0.25, 0.3 and 0.4 ml, respectively. The distension was stopped and the volume was kept constant for 2 min to induce stress relaxation. The pressure in the bag, the afferent discharge (spike rate) and the diameter of the segment during the relaxation time were recorded simultaneously.ResultsThe afferent discharge responses to distension showed a pattern with a peak during the sudden loading followed by decreasing activity with time. At distension volumes of 0.2, 0.25, 0.3 and 0.4 ml, the afferent discharge declined faster and to a greater extent (94%, 91%,96% and 87%) than the stress decreased (55%, 45%, 59% and 56%) during stress relaxation (p<0.001). Both the stress and the afferent discharge during the constant volume distension were independent of the distension volumes (p>0.5). The stress and the afferent discharge during the distension can be described mathematically on the basis of the quasi-linear theory of viscoelasticity. The association between the stress and the afferent discharge during the constant volume distension is linear with the same slope under various distension volumes.ConclusionsIntestinal mechanoreceptors were sensitive to the stress stimulus and a linear association between the stress relaxation and afferent discharge adaptation was found. The quasi-linear theory of visco-elasticity can be transferred to analysis of mechanical stimulus evoked afferent discharge.     

Sympathetic and cardiovascular responses to venous distension in an occluded limb

We recently showed that a fixed volume (i.e., 40 ml) of saline infused into the venous circulation of an arterially occluded vascular bed increases muscle sympathetic nerve activity (MSNA) and blood pressure. In the present report, we hypothesized that the volume and rate of infusion would influence the magnitude of the sympathetic response. Blood pressure, heart rate, and MSNA were assessed in 13 young healthy subjects during forearm saline infusions (arrested circulation). The effects of different volumes of saline (i.e., 2%, 3%, 4%, or 5% forearm volume at 30 ml/min) and different rates of infusion (i.e., 5% forearm volume at 10, 20, or 30 ml/min) were evaluated. MSNA and blood pressure responses were linked with the infusion volume. Infusion of 5% of forearm volume evoked greater MSNA responses than did infusion of 2% of forearm volume (Δ11.6 ± 1.9 vs. Δ3.1 ± 1.8 bursts/min and Δ332 ± 105 vs. Δ38 ± 32 units/min, all P < 0.05). Moreover, greater MSNA responses were evoked by saline infusion at 30 ml/min than 10 ml/min (P < 0.05). Sonographic measurements confirmed that the saline infusions induced forearm venous distension. The results suggest that volume and rate of saline infusion are important factors in evoking sympathetic activation. We postulate that venous distension contributes to cardiovascular autonomic adjustment in humans.     

Pharmacological analysis of components of the change in transmural potential difference evoked by distension of rat proximal small intestine in vivo

The reflex response to distension of the small intestine in vivo is complex and not well understood. The aim of this study was to characterize the neural mechanisms contributing to the complex time course of the intestinal secretory response to distension. Transmucosal potential difference (PD) was used as a marker for mucosal chloride secretion, which reflects the activity of the secretomotor neurons. Graded distensions (5, 10, and 20 mmHg) of distal rat duodenum with saline for 5 min induced a biphasic PD response with an initial peak (rapid response) followed by a plateau (sustained response). The rapid response was significantly reduced by the neural blockers tetrodotoxin and lidocaine (given serosally) and by intravenous (iv) administration of the ganglionic blocker hexamethonium and the NK(1) receptor antagonist SR-140333. Serosal TTX and iv SR-140333 significantly reduced the sustained response, which was also reduced by the NK(3) receptor antagonist talnetant and by the vasoactive intestinal polypeptide (VPAC) receptor antagonist [4Cl-d-Phe(6), Leu(17)]-VIP. Serosal lidocaine and iv hexamethonium had no significant effect on this component. Inhibition of nitric oxide synthase had no effect on any of the components of the PD response to distension. The PD response to distension thus seems to consist of two components, a rapidly activating and adapting component operating via nicotinic transmission and NK(1) receptors, and a slow component operating via VIP-ergic transmission and involving both NK(1) and NK(3) receptors.     

Effect of NOS inhibition on central response to atrial distension during pregnancy

Atrial distension increases c-fos expression in the paraventricular nucleus of virgin, but not pregnant, rats. We proposed that nitric oxide (NO), biosynthesis of which increases during pregnancy, blunts this reflex and that blocking NO biosynthesis would restore the response. Female rats were implanted with indwelling intracardiac balloons. On day 14 of pregnancy, osmotic minipumps containing either D- or N(G)-nitro-L-arginine methyl ester (L-NAME) (120 mg/2 ml at 10 microg/min) were implanted. On day 20, the rats were infused with saline (3 ml/h) with or without atrial balloon inflation (1 h). The brains were then processed for quantitation of c-fos expression. In the virgin rats, and in the pregnant rats treated with L-NAME, atrial distension significantly increased hypothalamic c-fos expression. In the pregnant animals treated with D-NAME, the response was greatly attenuated. NO had no effect on the increase in atrial receptor afferent discharge (single-fiber recordings) elicited by atrial distension. We conclude that, during pregnancy, NO attenuates central processing of the reflex response to atrial distension but does not alter the transducer properties of the volume receptors.