Vagal esophageal receptors in anesthetized dogs: mechanical and chemical responsiveness.
(9/2742)
This study was performed to evaluate the characteristics of esophageal receptors in anesthetized and artificially ventilated dogs. The electrical activity of the esophageal afferents was recorded from the peripheral cut end of the cervical vagus nerve. A cuffed catheter was inserted into the esophagus at the level of the third tracheal ring and was used to establish the esophageal location of the endings. Most of the receptors were localized in the intrathoracic portion of the esophagus. The majority of the receptors studied (36 of 43) showed a slow adaptation to a maintained stretch of the esophageal wall. Vagal cooling blocked receptor activity at temperatures ranging from 3.5 to 25 degrees C. Twenty-eight of 43 receptors, including 4 rapidly adapting endings (RAR), were challenged with saline, HCl + pepsin (HCl-P; pH 1) and distilled water (8 ml, 37 degrees C). HCl-P solutions specifically stimulated only three receptors; saline or water did not. Five slowly adapting receptors and two RARs were also challenged with topically applied capsaicin; only one RAR was stimulated. To ascertain a possible effect of smooth muscle contraction, 17 receptors were tested with intravenous injections of ACh and/or asphyxia; only 4 were stimulated. These characteristics do not support an important reflexogenic role of the esophagus in response to chemical stimuli. (+info)
Vagus nerve modulates secretin binding sites in the rat forestomach.
(10/2742)
Secretin is well known for its inhibitory action on gastric motility. It has been reported that secretin in a physiological dose inhibits gastric motility through mediation by the vagal afferent pathway. Secretin also elicited relaxation of carbachol-stimulated rat forestomach muscle strips by binding to its receptors, suggesting a direct action on this peripheral tissue. We hypothesized that vagal input may affect the action of secretin by modulating the level of secretin receptor in the forestomach. Several treatments, including vagal ligation, vagotomy, perivagal application of capsaicin or colchicine, intravenous infusion of tetrodotoxin, and intraperitoneal injection of atropine, were performed to investigate their effects on secretin receptor binding to forestomach membranes. Specific binding of 125I-labeled secretin to forestomach membranes was significantly decreased (45%) by vagal ligation, vagotomy (50%), or perivagal colchicine treatment (40%). On the contrary, specific binding of 125I-secretin was not affected by perivagal capsaicin treatment, intravenous infusion of tetrodotoxin, or intraperitoneal injection of atropine. By Scatchard analysis of the binding data, the capacity of the high-affinity binding sites in forestomach membranes was found to decrease significantly after vagal ligation compared with membranes from the sham-operated group. However, the affinity at the high-affinity binding sites, the binding parameters of the low-affinity binding sites, and binding specificity were not changed. Vagal ligation but not perivagal capsaicin treatment reduced the inhibitory effect of secretin on bethanechol-stimulated contraction of isolated forestomach muscle strips, causing a right shift in the dose-response curve. These results suggest that vagal input through axonal transport plays a significant role on secretin action by modulating the capacity of secretin binding sites (but not affinity or specificity), at least in rat forestomach. (+info)
Estrogen enhancement of baroreflex sensitivity is centrally mediated.
(11/2742)
We have recently shown that estrogen enhances baroreceptor control of reflex bradycardia in conscious rats. The present study replicated this finding in pentobarbital sodium-anesthetized rats, and the study was extended to investigate whether this effect of estrogen is centrally or peripherally mediated. Hemodynamic responses to electrical stimulation of the central end of the aortic depressor or the vagal efferent nerve were evaluated in pentobarbital sodium-anesthetized sham-operated (SO), ovariectomized (OVX), and OVX estradiol-treated Sprague-Dawley rats. Phenylephrine (1-16 microgram/kg iv) elicited dose-dependent pressor and bradycardic responses. Regression analysis of the baroreflex curves, relating changes in mean arterial pressure and heart rate, revealed a significantly smaller baroreflex sensitivity in OVX compared with SO anesthetized rats (-0.54 +/- 0.05 and -0.91 +/- 0.12 beats. min-1. mmHg-1, respectively; P < 0.05). Treatment of OVX rats with 17beta-estradiol (E2, 50 microgram. kg-1. day-1 for 2 days subcutaneously) significantly enhanced baroreflex sensitivity to a level similar to that of SO rats (P < 0.05). The enhancing effect of E2 on the baroreflex-mediated bradycardia, observed in conscious and anesthetized rats, seems to be selective because the baroreflex-mediated tachycardic responses measured in a separate group of conscious rats were not altered by ovariectomy or E2 administration. Electrical stimulation of the aortic nerve elicited frequency-dependent depressor and bradycardic responses that were significantly smaller in OVX compared with SO values (P < 0.05). Treatment of OVX rats with E2 restored the hemodynamic responses to aortic stimulation to near SO levels. On the other hand, hemodynamic responses to vagal stimulation were not affected by OVX or treatment with E2. These findings suggest that enhancement of reflex bradycardia by estrogen is centrally mediated and involves interaction with central projections of the aortic nerve. (+info)
Influence of right atrial pressure on the cardiac pacemaker response to vagal stimulation.
(12/2742)
We have recently shown that the intrinsic rate response to an increase in right atrial pressure is augmented when cardiac muscarinic receptors are activated. This present study examines the cardiac pacemaker response to vagal stimulation at different values of right atrial pressure in isolated rat right atrium and in the rabbit heart in situ. In the rat atrium, when pressure was raised in steps from 2 to 10 mmHg, there was a progressive reduction in the response to vagal stimulation [40.5 +/- 7.2% reduction (mean +/- SE) at 8 mmHg, P < 0.01], which was independent of the level of vagal bradycardia, that persisted in the presence of the beta-adrenergic agonist isoproterenol. In barbiturate-anesthetized rabbits with cervical vagi cut and beta-adrenergic blockade, raising right atrial pressure approximately 2.5 mmHg by blood volume expansion reduced the bradycardia elicited by electrical stimulation of the peripheral end of the right vagus nerve (9.1 +/- 1.1% reduction, P < 0.0001). These results demonstrate that vagal bradycardia is modulated by the level of right atrial pressure and suggest that normally right atrial pressure may interact with cardiac vagal activity in the control of heart rate. (+info)
Altered airway and cardiac responses in mice lacking G protein-coupled receptor kinase 3.
(13/2742)
Contraction and relaxation of airway smooth muscles is mediated, in part, by G protein-coupled receptors (GPCRs) and dysfunction of these receptors has been implicated in asthma. Phosphorylation of GPCRs, by G protein-coupled receptor kinase (GRK), is an important mechanism involved in the dampening of GPCR signaling. To determine whether this mechanism might play a role in airway smooth muscle physiology, we examined the airway pressure time index and heart rate (HR) responses to intravenous administration of the cholinergic agonist methacholine (MCh) in genetically altered mice lacking one copy of GRK2 (GRK2 +/-), homozygous GRK3 knockout (GRK3 -/-), and wild-type littermates. (GRK2 -/- mice die in utero.) GRK3 -/- mice demonstrated a significant enhancement in the airway response to 100 and 250 microgram/kg doses of MCh compared with wild-type and GRK2 +/- mice. GRK3 -/- mice also displayed an enhanced sensitivity of the airway smooth muscle response to MCh. In addition, GRK3 -/- mice displayed an altered HR recovery from MCh-induced bradycardia. Although direct stimulation of cardiac muscarinic receptors measured as vagal stimulation-induced bradycardia was similar in GRK3 -/- and wild-type mice, the baroreflex increase in HR associated with sodium nitroprusside-induced hypotension was significantly greater in GRK3 -/- than wild-type mice. Therefore, these data demonstrate that in the mouse, GRK3 may be involved in modulating the cholinergic response of airway smooth muscle and in regulating the chronotropic component of the baroreceptor reflex. (+info)
Sympathovagal balance is major determinant of short-term blood pressure variability in healthy subjects.
(14/2742)
Short-term blood pressure variability (BPV) has been suggested to provide important information about cardiovascular regulation. However, the background of BPV, its determinants, and physiological correlates have remained obscure. The aim of this study was to characterize physiological correlates of BPV and to investigate associations between BPV and neural and hormonal regulatory systems at rest in healthy subjects. We studied 117 healthy, normal-weight, nonsmoking male and female subjects aged 23-77 yr. Spectral analysis of BPV and heart rate variability (HRV) was performed from 5-min blood pressure (Finapres) and electrocardiogram recordings during controlled breathing. Baroreflex sensitivity (BRS) was measured using the phenylephrine method. In addition, plasma concentrations of norepinephrine, epinephrine, and arginine vasopressin and plasma renin activity were measured. We found that the ratio between the low- and high-frequency components of HRV, an index of cardiac sympathovagal balance, correlated positively with total power and very low- and low-frequency components of systolic and diastolic BPV and inversely with high-frequency components of systolic and diastolic BPV. BRS, predominantly a measure of cardiac vagal regulation, correlated inversely with BPV. Furthermore, age, gender, body mass index, and systolic blood pressure contributed to BPV. Vasoactive hormones were not significant correlates of BPV. We conclude that sympathovagal balance of cardiovascular regulation is the major determinant of BPV. Other factors associated with BPV are age, gender, body mass index, blood pressure, and BRS. (+info)
Sympathovagal balance: how should we measure it?
(15/2742)
There are complex interactions between the sympathetic and parasympathetic nervous system inputs to the sinus node. The concept of "sympathovagal balance" reflects the autonomic state resulting from the sympathetic and parasympathetic influences. Despite widespread usage of a variety of heart rate (HR) variability parameters as indexes of sympathovagal balance, no index has been validated as a measure of sympathovagal balance. This study evaluated the utility of HR, HR variability, and a new parameter termed the vagal-sympathetic effect (VSE) as indexes of sympathovagal balance. The ideal parameter had to satisfy the following criteria: 1) the index should vary similarly among subjects in response to different autonomic conditions; 2) the variability in the index among subjects exposed to the same autonomic conditions should be small; and 3) the response of the index to various autonomic conditions should reflect the underlying changes in physiological state and have a meaningful interpretation. Volunteers [8 men, 6 women; mean age 28.5 +/- 4.8 (SD) yr] were evaluated for the effects of sympathetic and parasympathetic stimulation and blockade on HR and HR variability. VSE was defined as the ratio of the R-R interval to the intrinsic R-R interval. VSE and R-R interval consistently changed in the expected directions with parasympathetic and sympathetic stimulation and blockade. A general linearized model was used to evaluate the response of each parameter. VSE and R-R interval had r2 values of 0.847 and 0.852, respectively. Natural logarithm of the low-frequency power had an r2 value of 0.781 with lower r2 values for all the other HR variability parameters. The coefficient of variation was also lowest for each condition tested for the VSE and the R-R interval. VSE and R-R interval best satisfy the criteria for the ideal index of sympathovagal balance. Because it is impractical under most conditions to measure the VSE as the index of sympathovagal balance, the most suitable index is the R-R interval. (+info)
Vagotomy inhibits the jejunal fluid secretion activated by luminal ileal Escherichia coli STa in the rat in vivo.
(16/2742)
BACKGROUND: Escherichia coli heat stable enterotoxin (STa) is a major cause of secretory diarrhoea in humans. AIMS: To assess the effects of instilling STa into the ileum on remote fluid secretion in the jejunum and colon in rats in vivo by a gravimetric technique. METHODS AND RESULTS: Ileal STa (55 ng/ml) stimulated fluid secretion in both ileal and jejunal loops but not in the colon. The fluid secretion induced by ileal STa was inhibited by L-NAME (Nomega-nitro-L-arginine methyl ester, 40 mg/kg intraperitoneally) but not by D-NAME (Nomega-nitro-D-arginine methyl ester). Ileal carbachol (183 mg/ml) instilled into the lumen stimulated ileal secretion but not jejunal secretion, and was unaffected by L-NAME. Capsaicin (10 microM), instilled luminally with STa in the ileum, blocked both the ileal and jejunal fluid secretion. Acute bilateral vagotomy prevented luminal ileal STa from inducing jejunal fluid secretion but not from activating ileal fluid secretion. CONCLUSION: Ileal E coli STa stimulates remote secretion in the rat jejunum but not in the colon, probably by a nitrinergic, vagal reflex mediated by C fibres. This neural pathway will amplify the action of the toxin in its generation of secretory diarrhoea. (+info)