Tonic Contractile Activity Research Articles

ROLE OF THROMBOXANE AND LEUKOTRIENES IN MECHANISMS OF CONTRACTILE REACTIONS OF PORTAL VEIN, INDUCED BY ACETYLCHLINE AND PHENYLEPHRINE

Effects of picotamide and zileuton on tonic contractile activity of the rat portal vein preparations, induced by acetylcholine (2.10(-5) mol/1) and phenylephrine (5.10(-7) mol/1) were investigated. Conversion of arachidonic acid products (prostaglandins, leukotrienes) synthesized by endothelial cells, plays an important role in the local regulation of vascular tone. The compounds formed in a cascade of enzymatic transformations can modulate the effect of other vasoactive factors. Picotamide (6,5.10(-5) mol/1) - thromboxane receptor and thromboxane -synthase blocker - depress acetylcholine-induction tonic contraction of isolated segments of portal vein with intact endothelium by 29% and norepinephrine-induction reduction of 45% relative to the control values. The obtained results indicate a participation of thromboxane and/or endoperoxide H2 in this reaction. Partial inhibition of the contractions by 5-lipoxygenase blocker zileuton(4,2.10(-5) mol/1) at 23% relative to control values suggests, that products of lipoxigenase pathways of arachidonic acid conversion are involved in mechanisms of specified reactions. These data indicate complex mechanisms of regulation of vascular tone of the portal vein, which play an important role eicosanoids. Further study of these mechanisms is necessary for the formation of basic knowledge, as well as to elucidate the mechanisms of occurrence and development of pathological conditions of vessels and the development of methods of their correction.

Участь ейкозаноїдів у механізмі скоротливих реакцій ворітної вени на дію адреналіну і норадреналіну

The influence of indometacine (7 x 10(-8)M) on the tonic contractile activity of the isolated rat portal vein (PV) under the action of adrenaline (1 x 10(-5)M) and noradrenaline (5 x 10(-6)M) was studied. Indometacine decreased the amplitude of noradrenaline-induced tonic constriction of PV with intact endothelium and produced no effect on constriction of vessels with denuded endothelial layer. The results suggest that these reactions are mediated by endothelial prostanoids. Inhibition of adrenaline-induced constriction of PV preparations with intact and denuded endothelium suggests that the contractile reactions are mediated by prostanoides derived from both endothelial and smooth muscle cells.

Contractile activity of the bladder urothelium/lamina propria and its regulation by nitric oxide

In the bladder, nitric oxide (NO) is released from neuronal and non-neuronal sources, but its actions are unclear. Strips of urothelium plus lamina propria contract in response to agonists and develop spontaneous phasic contractions, and the aim of this study was to investigate the influence of NO on this activity. Isolated strips of urothelium/lamina propria from porcine bladder developed spontaneous contractions (3.5±0.3cycles/min) and contracted in response to carbachol and electrical field stimulation (EFS). The NO synthase inhibitor Nω-nitro-l-arginine (L-NNA, 100μM) had no effects on the tissues, but the NO donors diethylamine NONOate (DEANO, 100μM) and nitroprusside (10μM) caused relaxation, slowed the spontaneous rate of contractions and inhibited responses to carbachol. Maximum tonic contractions to carbachol were reduced by 17±4% (P<0.001) and 35±5% (P<0.001) by DEANO and nitroprusside respectively and the potency of carbachol was also reduced. Carbachol also increased the spontaneous frequency of contraction and these rate responses were again inhibited by DEANO and nitroprusside, but unaffected by L-NNA. Similarly, responses to EFS were significantly depressed (52–70%) by DEANO (P<0.05), but were unaffected by L-NNA. These data demonstrate spontaneous contractile activity and also nerve and agonist-induced tonic contractile activity within the urothelium and lamina propria. This activity is sensitive to depression by NO, but NO does not appear to be spontaneously released to influence this activity, nor does it appear to be released by muscarinic receptor stimulation. However the results suggest that in situations where NO production is increased, NO can influence the contractile activity of this tissue.

Neural regulation of tone in the oesophageal body: in vivo barostat assessment of volume-pressure relationships in the feline oesophagus.

Recent combined manometric-barostat studies demonstrated that the oesophageal body exhibits both peristaltic contractions and tone. This study further characterized the neural modulation of tone in the feline oesophageal body. Simultaneous oesophageal barostat and manometry were performed in 20 adult cats under ketamine sedation. Oesophageal tone and peristalsis were assessed in the distal smooth muscle oesophagus. Cholinergic modulation was studied using neostigmine, erythromycin, atropine and vagotomy. Nitrergic regulation was assessed using sildenafil to increase cellular cyclic guanosine monophosphate and the nitric oxide synthase blocker Nomega-nitro-l-arginine (l-NNA). The presence of a tonic contractile activity in the distal oesophageal body was confirmed. Peristaltic contractions proceeded along the oesophageal body over the background tonic contraction. Neostigmine and erythromycin enhanced (20-30%) whereas bilateral vagotomy and atropine strongly decreased oesophageal tone (50-60%). However, l-NNA increased (40%) and sildenafil decreased oesophageal tone (30%). Therefore, tonic contractile activity in the oesophageal body is mainly caused by a continuous cholinergic excitatory input. A nitric oxide inhibitory mechanism may have a complementary role in the regulation of oesophageal tone.

Effect of histamine on phasic and tonic contractions of isolated uterine tissue from pregnant women

Objective: To enhance our understanding of the uterotonic effect of histamine, we compared the effects of histamine on spontaneous phasic and tonic contractile activity of uterine strips from term pregnant nonlaboring women. Study Design: Longitudinal uterine strips were used from the lower uterine segment of term pregnant nonlaboring women undergoing elective cesarean section. The concentration-response relationship to histamine (10–8 to 10–4 mol/L) was determined in spontaneously contracting strips or in strips contracted tonically with a protein kinase C activator (–)–indolactam V in the presence of H1 receptor antagonist (S[+]-chlorpheniramine maleate), H2 receptor antagonist (cimetidine), or solvent. Results: Histamine increased spontaneous phasic myometrial contractions in a concentration-dependent manner. H1, but not H2, receptor antagonist significantly attenuated the response to histamine. Histamine significantly reduced tonic contractions of uterine strips induced by indolactam V. H1 histamine receptor antagonist abolished relaxation, whereas H2 histamine receptor antagonist had no effect. Conclusion: Histamine increases spontaneous, but inhibits tonic, contractions of uterine strips from term pregnant nonlaboring women. Both effects are mediated through activation of H1 receptors. (Am J Obstet Gynecol 2003;188:774-8.)

Motor abnormality in the gastroduodenal junction in patients with infantile hypertrophic pyloric stenosis

Background/Purpose: Periodic clusters of phasic pressure waves in the gastroduodenal junction (GDJ) have been seen in patients with infantile hypertrophic pyloric stenosis (IHPS). This study investigated the details of these pressure waves in relation to disturbed transpyloric flow in IHPS. Methods: Manometric study was performed in 11 IHPS patients before and after atropine therapy and 2 non-IHPS infants. Pressure changes in the GDJ were measured with an 8-channel sleeve or a 9-channel sidehole micromanometric assembly under fluoroscopic control for 2 hours. Results: Clusters of phasic pressure waves (365 ± 42 mm Hg) associated with an increase in basal pressure (10 ± 3 mm Hg) were intermittently observed in the GDJ in all IHPS patients. Similar observations were not made in the non-IHPS infants. Most antral pressure waves occurred simultaneously with those pressure waves in the GDJ in the IHPS patients. Atropine (0.01 mg/kg) transiently abolished the phasic and tonic pressure waves for 19 ± 10 minutes. Significantly fewer phasic pressure waves were observed after atropine therapy. Conclusions: Characteristic phasic and tonic contractile activity in the GDJ is uncoordinated with the antral contractions in IHPS patients. Such incoordination may be an important factor in the disturbed transpyloric flow in IHPS. J Pediatr Surg 36:1641-1645. Copyright © 2001 by W.B. Saunders Company.

Depressed smooth muscle contractility after massive intestinal resection in rat: role of alterations in muscarinic receptor status or source of calcium for excitation-contraction coupling.

Following massive intestinal resection (removal of 75% of the mid-jejunoileum) in the rat, there is a significant reduction in the in vitro tonic contractile response of the remaining jejunal circular smooth muscle in response to stimulation with the muscarinic agonist bethanechol. The aim of these experiments was to determine if this alteration is specific to muscarinic excitation and occurs as a result of changes in the source and availability of calcium required for excitation-contraction coupling, or reflects changes in muscarinic receptor number and (or) affinity. The contractile response of proximal jejunal circular muscle strips from sham-operated and resected rats was studied in vitro in response to electrical field stimulation, serotonin, and bethanechol, the later under conditions where extracellular calcium was absent or entry was excluded. In contrast with the significant reduction in tonic contractile response to muscarinic excitation of tissues from resected animals, there was an equivalent or enhanced response of these tissues to electrical field stimulation and serotonin, respectively. While sham-operated and resected groups showed similar dependency upon or availability of intracellular and extracellular calcium, the data indicate distinct pathways of calcium mobilization for tonic versus phasic contractile activity. Muscarinic receptor number and affinity were assessed by 1-quinuclidinyl[pheny1-4-3H]benzilate ([3H]QNB) binding to isolated smooth muscle cells and showed a significant increase in Bmax, with no change in Kd after resection. Thus, the reduced contractility of the circular muscle of the remnant jejunum after massive intestinal resection is a specific even associated with muscarinic receptor activation, but it is not the result of either an alteration in the source or availability of calcium required for excitation-contraction coupling or a reduction in the number and (or) affinity of muscarinic receptors.

Massive intestinal resection depresses circular smooth muscle contractility in the rat.

To determine whether functional changes in in vitro contractility and in vivo gastrointestinal transit accompany the adaptive structural changes seen in jejunal circular muscle after massive intestinal resection, rats were subjected to either surgical resection of 75% of the mid-jejunoileum or a sham operation. Basal stress in response to stretch was similar for both groups on postoperative days 10, 20, 30, and 40. By day 10 after surgery, tissues from resected rats exhibited a significant reduction in bethanechol-stimulated tonic stress and in frequency of phasic contractions. The amplitude of spontaneous phasic activity was significantly increased; however, following cholinergic stimulation, the magnitude of the increase in the amplitude of phasic activity was significantly reduced. Experiments with tetrodotoxin (10(-6) M) indicated a myogenic origin to the reduction in bethanechol-stimulated tonic stress and the reduced frequency and altered amplitude of phasic contractile activity in resected animals. The tonic stress developed in response to depolarization with KCl did not differ significantly between sham-operated and resected rats. Transit studies showed no change in the rate of gastric emptying after resection but did reveal a significant reduction in the velocity of intestinal transit. Thus, following massive intestinal resection the bethanechol-stimulated tonic stress response and phasic contractile activity of circular smooth muscle are significantly reduced, concomitant with altered intestinal transit. The reduction in contractility in the resected animals may be due to an alteration at the level of the smooth muscle receptor and (or) its signal transduction pathway.

Different muscarinic receptor subtypes mediating the phasic activity and basal tone of pig isolated intravesical ureter

1. We have studied the effects of muscarinic cholinoceptor agonists and specific antagonists on both phasic activity and basal tone of the isolated intravesical ureter of the pig by means of isometric techniques in vitro. 2. Acetylcholine in the presence and absence of physostigmine increased both phasic activity and basal tone of ureteral strips in a concentration-dependent manner. Moreover carbachol, methacholine and oxotremorine-M increased both contractile parameters while bethanechol and McN-A-343 evoked only increases in tone without affecting the frequency of the phasic contractions. 3. The nicotinic receptor blocker, hexamethonium (10(-6)-10(-4) M), failed to modify the contractions evoked by a single dose of carbachol (10(-5) M), whilst the muscarinic antagonist, atropine inhibited both phasic and tonic responses. 4. The muscarinic M1 (pirenzepine), M2 (AF-DX 116 and methoctramine), M3 (4-DAMP, HHSiD and p-F-HHSiD), and putative M4 receptor (tropicamide) antagonists significantly reversed increases in both frequency of phasic activity and baseline tone induced by a submaximal dose of carbachol (10(-5) M). The pIC50 values for inhibition of the induced phasic activity were: atropine (10.16) > 4-DAMP (9.12) > HHSiD (8.22) = methoctramine (7.98) = p-F-HHSiD (7.88 > tropicamide (7.62) = pirenzepine (7.53) = AF-DX 116 (7.45) and for inhibition of basal tone were: atropine (10.73) > 4-DAMP (9.32) > HHSiD (8.65) = pirenzepine (8.43) = p-F-HHSiD (8.38) > methoctramine (7.79) > tropicamide (7.53) > AF-DX 116 (7.04). 5. The antagonist profile indicates that an M1 receptor mediates the tonic response while the phasic activity could involve either both M2 and M3 or an M4 muscarinic receptor. These results suggest that different muscarinic receptor subtypes mediate the phasic and tonic contractile activity induced by a submaximal concentration of carbachol in the porcine intravesical ureter.

Phasic and tonic contractile activity in human coronary artery in vitro

Phasic and tonic contractile activity in human coronary artery in vitro

Mitochondrial biogenesis in striated muscles: rapid induction of citrate synthase mRNA by nerve stimulation

Tonic contractile activity induces mitochondrial biogenesis in mammalian skeletal muscles, necessitating regulation of both nuclear and mitochondrial genes encoding mitochondrial proteins. In this study we compared the time course of induction of citrate synthase (CS) mRNA, a nuclear gene product, to that of genes encoded by mitochondrial DNA during the adaptive response to indirect nerve stimulation in tibialis anterior muscles of adult rabbits. A CS cDNA probe was prepared from a rabbit heart cDNA library by the polymerase chain reaction using synthetic oligonucleotide primers based on the published sequence of the porcine gene. This cDNA probe hybridized to a single band on Northern blots of total or polyadenylated RNA from adult rabbit tissues. Nerve stimulation for 3 days increased the abundance of CS mRNA relative to total cellular RNA by 2.3 +/- 0.2-fold (mean +/- SE, n = 8; P less than 0.01). In contrast, CS enzyme activity and mitochondrial RNA transcripts were not significantly increased at this time point. However, when nerve stimulation was continued for 21 days, the increases in CS mRNA and mitochondrial RNAs were similar. These results support the hypothesis that genetic signaling mechanisms triggered by neural input are sensed initially within the nucleus and that expression of mitochondrial genes is regulated as a secondary event.

Increased expression of fibroblast growth factors in a rabbit skeletal muscle model of exercise conditioning.

Increased tonic contractile activity from exercise or electrical stimulation induces a variety of changes in skeletal muscle, including vascular growth, myoblast proliferation, and fast to slow fiber type conversion. Little is known about the cellular control of such changes, but pleiotropic biochemical modulators such as fibroblast growth factors (FGFs) may be involved in this response and thus may be regulated in response to such stimuli. We examined the regulation of FGF expression in an in vivo model of exercise conditioning previously shown to exhibit vascular growth and fast to slow fiber conversion. FGFs were extracted by heparin-affinity chromatography from extensor digitorum longus muscles of adult rabbits subjected to chronic motor nerve stimulation at 10 Hz. Growth factor activity (expressed in growth factor units [GFUs]) of muscle stimulated for 3 and 21 d was assayed by [3H]thymidine incorporation in 3T3 fibroblasts and compared with that present in the contralateral unstimulated muscle. A small increase in heparin-binding mitogenic activity was observed as early as 3 d of stimulation, and by 21 d mitogenic activity increased significantly when normalized to either wet weight (stimulated, 287 +/- 61 GFU/g; unstimulated, 145 +/- 39 GFU/g) or to protein (stimulated, 5.3 +/- 1.1 GFU/mg; unstimulated, 2.2 +/- 0.6 GFU/mg) (+/- SE, P less than 0.05). Western analysis demonstrated increased amounts of peptides with immunological identity to acidic and basic FGFs in stimulated muscle. The increase in FGF content observed in this study is synchronous with neovascularization, myoblast proliferation, and fast to slow fiber type conversion previously shown in this model. These results demonstrate that increased expression of FGFs is associated with motor nerve stimulation and increased tonic contractile activity of skeletal muscle, and suggests that these proteins may play a regulatory role in the cellular changes that occur during exercise conditioning.

Activity-induced adaptations in skeletal muscles of iron-deficient rabbits.

The purpose of this study was to determine whether severe iron deficiency alters the adaptive response of skeletal muscle fibers to a sustained increase in tonic contractile activity. Seven weanling rabbits consumed a low iron diet and underwent phlebotomy twice weekly for 6 mo, resulting in severe anemia (mean Hb 5.5 g/dl). Compared with control animals, tibialis anterior skeletal muscles of iron-deficient animals exhibited reduced concentrations of cytochrome c (4.4 +/- 0.7 vs. 8.6 +/- 0.7 nmol/g tissue; P less than 0.01), and reduced activities of citrate synthase (83 +/- 10 vs. 133 +/- 13 mU/mg protein; P less than 0.01) and cytochrome-c oxidase (2.2 +/- 0.2 vs. 3.6 +/- 0.5 U/mg protein; P less than 0.05). In these muscles mitochondria were swollen and displayed deformed cristae. Less severe biochemical abnormalities were observed in cardiac and soleus skeletal muscles. Ten days of continuous electrical stimulation of the motor nerve supplying anterior compartment muscles of iron-deficient rabbits increased expression of mitochondrial proteins: cytochrome c was increased to 154% of control levels (P less than 0.05), and cytochrome-c oxidase and citrate synthase activities were increased to 199 and 272% of control levels, respectively (P less than 0.005). In addition, electrical pacing increased the fractional volume of mitochondria observed by electron microscopy and reduced the activity of aldolase A by 28% (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Manometric Evaluation of Functional Upper Gut Symptoms

Pressure activity in the stomach and upper intestine was studied in 104 patients referred to the Mayo Clinic for evaluation of functional symptoms (nausea, vomiting, upper abdominal pain, or other dyspeptic symptoms in the absence of structural gut abnormalities). Manometric abnormalities were found in 75 patients. Forty-three of these had gastric abnormalities and 32 patients had both gastric and intestinal abnormalities. In the stomach, decreased antral phasic pressure activity after a solid meal was the most common abnormality. In the upper intestine, unpropagated bursts of phasic and tonic contractile activity were a relatively frequent abnormality but a number of other altered manometric patterns also were observed. Digestive tract symptoms were not good predictors of the presence or site of the gastrointestinal manometric abnormalities. Patients with associated neurologic, urologic, or metabolic (diabetes) disease were more likely to exhibit manometric abnormalities than were those without evidence of disease outside the gut. Almost two-thirds of the patients with symptoms and normal manometry presented features suggestive of psychiatric disease. We conclude that in patients with severe functional-type symptoms gastrointestinal manometry is a useful technique to evidence the underlying gut motor disturbance that is present in a relatively high proportion of these patients.

Electrical basis of contractions in the muscle layers of the pig colon.

Simultaneous in vitro measurements of electrical and mechanical activities were performed, using suction electrodes and force transducers, respectively, on longitudinal and circular muscle layers of the pig proximal colon. In addition, circular muscle strips were studied with the sucrose gap technique. Spontaneous activity was present in both preparations. In the circular muscle, slow waves with superimposed spikes occurred at a variable frequency, accompanied by phasic contractions. Longitudinal muscle preparations showed a different behavior. Regular appearance of distinct slow waves as described for the circular muscle did not occur. Instead, periods of membrane potential oscillations at a frequency of 41 cycles/min and a duration of approximately 12 s were observed in this layer. Most oscillations had superimposed spikes, and each period of oscillations was associated with a contraction. Spontaneous activity in the circular layer was myogenic in nature but susceptible to innervation and stretch. In contrast, an excitatory stimulus (acetylcholine or stretch) was a prerequisite for activity in the longitudinal layer. Cholinomimetics increased and adrenergic agents decreased the frequency of the slow waves and spiking activity and frequency and force of contractions in the circular muscle. Cholinergic agents increased the activity in the longitudinal muscle into continuous electrical oscillations with spiking activity and concomitant tonic contractile activity, whereas adrenergic agents abolished electrical and mechanical activity. Spontaneous release of acetylcholine occurred, partly due to regenerative activity of myenteric cholinergic nerves. In addition, tonic activity in the noncholinergic nonadrenergic inhibitory neurons decreased circular muscle tone.