Spontaneous contractions of intestinal smooth muscle re-aggregates from the new-born rat triggered by thromboxane A2

Isolated smooth muscle cells from the small intestine of new-born rats were prepared by enzymatic digestion. These cells re-aggregate after 1 day in culture to clusters. The re-aggregates show spontaneous rhythmical contractions at 37 degrees C with a frequency (13.1 +/- 0.8 min-1, n = 49), which is similar to that of the intact smooth muscle layer. The cholinergic agonist carbachol (5 x 10(-5) mol l-1) caused an increase in the frequency of the spontaneous contractions often ending in a permanent contraction. A similar effect was achieved with the thromboxane A2 (TXA2) agonist, U-46619 (10(-5) mol l-1). In contrast, both the TXA2 receptor blocker, Bay u3405 (5 x 10(-4) mol l-1), as well as the Ca2+ channel blocker, verapamil (5 x 10(-5) mol l-1), suppressed the spontaneous contractions. The observed contractility was insensitive against the neuronal blocker tetrodotoxin (10(-6) mol l-1). These analyses of video images were supported by the measurement of relative changes in the intracellular Ca2+ concentration with the Ca(2+)-sensitive dye, fura-2. Spontaneous contractions were paralleled by spikes in the intracellular Ca2+ concentration, which were abolished by Bay u3405, but stimulated by U-46619 or carbachol. In summary, these results obtained at re-aggregates of intestinal smooth muscle cells support the hypothesis of a role of TXA2 in the generation of spontaneous intestinal smooth muscle contractions in vitro.     

Effect of sodium butyric acid, sodium valerianic acid, and osmolarity on contractility of specimens of intestinal wall obtained from the cecum and spiral colon of healthy cows

OBJECTIVE: To compare the effect of various concentrations of sodium butyric acid and sodium valerianic acid, as well as various osmolarities, on contractility of ex-vivo intestinal wall specimens obtained from the cecum and spiral colon of each of several healthy cows. SAMPLE POPULATION: Full-thickness preparations of intestinal wall, dissected parallel to the longitudinal smooth muscle layers, harvested from freshly slaughtered healthy cows. PROCEDURE: Specimens of intestinal wall were incubated for 5 minutes with various concentrations of sodium butyric acid and sodium valerianic acid as well as various osmolar concentrations of NaCl, using a crossover design. Isometric contractions were induced 7 times with carbachol (CH; 5 X 10(-6) mol/L). Contractility was defined as the maximum amplitude of contraction and the amplitude of contraction 2 minutes after addition of CH. RESULTS: Repeated addition of CH did not result in a significant effect on contractility of specimens from the cecum and spiral colon. Contractility after addition of CH was not significantly affected by prior incubation with various concentrations of sodium butyric acid or sodium valerianic acid or after an increase of osmolarity. Maximum amplitude of contraction was significantly higher in specimens from the spiral colon, compared with specimens from the cecum. CONCLUSIONS: Increases in concentrations of sodium butyric acid or sodium valerianic acid and increases in osmolarity did not inhibit contractility of intestinal wall specimens from the cecum and spiral colon of a group of healthy cows.     

In vitro investigation of the interaction between nitric oxide and cyclo-oxygenase activity in equine ventral colon smooth muscle

The objective of this study was to determine if a correlation exists between the presence of nitric oxide and prostaglandin release in the equine ventral colon smooth muscle, since this relationship may accentuate the inflammatory process during intestinal injury. Tissue was collected from the ventral colon, cut into muscle strips oriented along the circular, longitudinal and taenial layers, and mounted in a tissue bath system. Samples of the bath fluid were collected before, following electrical field stimulation (EFS), and following EFS in the presence of L-NAME, a nitric oxide synthase inhibitor. Muscle strips were also obtained following systemic administration of a cyclo-oxygnease inhibitor and samples were collected using the previously described protocol. Concentrations of prostaglandins were determined in the fluid samples using an ELISA. Electrical field stimulated release of nitric oxide produced a significant increase in prostaglandin production which did not occur in the presence of L-NAME. Systemic administration of flunixin meglumine reduced prostaglandin levels at all sampling periods, although a small increase was present following EFS. The results of this study support the hypothesis that there is a correlation between the release of nitric oxide and the production of prostaglandins in the smooth muscle of the large colon. This association between nitric oxide and prostaglandin may act as an important regulatory mechanism for various physiological mechanisms, such as vascular smooth muscle tone, and may contribute to amplified tissue injury when the induced forms of both enzymes are activated during an inflammatory insult. This suggests that the use and development of COX2 and iNOS inhibitors may help attenuate the inflammatory response following intestinal injury.     

Estrous cycle-dependent differences in responsiveness to prostaglandins and contractile agents in sheep (Ovis aries) cervical smooth muscle

We investigated the influence of the phase of the estrous cycle on mechanical responses elicited in sheep cervix by potassium chloride (KCl), acetylcholine chloride (ACh), prostaglandin F2 alpha (PGF2 alpha) and prostaglandin E1 (PGE1). The cervix of adult ewes (n = 48) were classified according to the presence or absence of corpora lutea (luteal or follicular phase, respectively). Muscle strips of the circular and longitudinal layers were prepared in an organ bath and coupled to an isometric force transducer. Concentration-response curves were obtained noncumulatively. KCl and ACh produced concentration-dependent contractions in all preparations in both phases of the estrous cycle. However, maximum effect, EC50 and slope values of KCl and ACh were not significantly different between muscle layers, as well as between the phases of the estrous cycle. The prostanoid, PGF2 alpha, produced a significant reduction in the amplitude of spontaneous contractions for all preparations. The depressant effect of PGF2 alpha on spontaneous contractions of circular smooth muscle was significantly greater during the follicular than the luteal phase, whilst the depressant effect of PGF2 alpha on the longitudinal layer did not differ between phases of the estrous cycle. PGE1 significantly reduced the amplitude of spontaneous contractions on circular but not on longitudinal preparations. In conclusion, we have characterized with in vitro preparations of circular and longitudinal muscle layers of ewes during the follicular and luteal phases of the estrous cycle, the parameters of the K- and ACh-induced contractions on cervix and the efficacy of PGF2 alpha and PGE1 on inhibition spontaneous contractile activity.     

Effects of trypsin on cytosolic calcium levels in the rat aortic endothelium

The effect of trypsin on vascular tone and the cytosolic calcium concentration ([Ca(2+)](i)) of endothelial and smooth muscle cells were examined in the rat aorta. A calcium indicator, fura-PE3, was used to measure [Ca(2+)](i) simultaneously with vascular tone. In the endothelium-intact rat aorta, carbachol and trypsin increased [Ca(2+)](i) in a dose-dependent manner. In the endothelium-denuded rat aorta, carbachol did not change [Ca(2+)](i), but trypsin slightly increased it. Addition of trypsin to the norepinephrine-stimulated rat aorta relaxed the muscle with an additional increase in [Ca(2+)](i). Under calcium-free conditions, trypsin induced a transient increase in [Ca(2+)](i). Trypsin-induced endothelium-dependent relaxation was inhibited by preincubation with l-NMMA, an endothelial NO synthase inhibitor, U-73122, a phospholipase C inhibitor, cyclopiazonic acid, a sarcoplasmic/endoplasmic reticulum Ca(2+)-ATPase blocker, and lanthanum, a nonselective Ca(2+) channel blocker. However, indomethacin, a nonselective cyclooxygenase inhibitor, and SKF-96365, a store-operated Ca(2+)-channel blocker, had no effect on the trypsin-induced relaxation. These results suggest that trypsin increases [Ca(2+)](i) in the endothelial cells through SKF-96365-insensitive Ca(2+) channels and regulates the release of NO, which results in relaxation of the rat aorta.     

In vitro effects of erythromycin, lidocaine, and metoclopramide on smooth muscle from the pyloric antrum, proximal portion of the duodenum, and middle portion of the jejunum of horses

OBJECTIVE: To evaluate effects of erythromycin, lidocaine, and metoclopramide on smooth muscle of the pyloric antrum (PA), proximal portion of the duodenum (PD), and middle portion of the jejunum (MJ) of horses. Sample Population-Strips of smooth muscle from 7 horses. PROCEDURE: Isolated muscle strips were suspended in a bath and attached to isometric force transducers. Once stable spontaneous contractions were observed, agents were added. Isometric stress responses were compared with the amplitude of spontaneous contractions. RESULTS: A single dose of erythromycin to the PA increased contractile amplitude (CA) for the longitudinal smooth muscle (mean +/- SEM, 76+/-16 g/cm2) but decreased CA for circular smooth muscle (-79+/-23 g/cm2). The inhibitory effect was decreased by tetrodotoxin, N(G)-nitro-L-arginine methyl ester, and a vasoactive intestinal peptide antagonist. Erythromycin increased CA for the MJ, which was maximal at 10(-4)M (171+/-36 g/cm2). Lidocaine increased CA for the PD, which was maximal at 10(-4) M (60+/-5 g/cm2). Metoclopramide increased the CA, which was maximal at 10(-4) M for the PA (75+/-26 g/cm2), PD (279+/-33 g/cm2), and MJ (456+/-59 g/cm2). CONCLUSIONS: Regional differences in responses to erythromycin, lidocaine, and metoclopramide were evident in the gastrointestinal tract of horses. Metoclopramide increased CA in all tissues used, whereas erythromycin inhibited CA in circular smooth muscle but stimulated CA in longitudinal smooth muscle from the PA. Inhibition is caused by stimulation of inhibitory nerves and is mediated, in part, by nitric oxide and vasoactive intestinal peptide.     

Cisapride Stimulates Contraction of Idiopathic Megacolonic Smooth Muscle in Cats

We have previously shown that cisapride, a substituted piperidinyl benzamide, stimulates contraction of healthy feline colonic smooth muscle. The purpose of the present investigation was to determine the effect of cisapride on feline idiopathic megacolonic smooth muscle function. Longitudinal smooth muscle strips from ascending and descending colon were obtained from cats with idiopathic megacolon, suspended in a 1.5 mM Ca²⁺-HEPES buffer solution (37°C, 100% O₂, pH 7.4), attached to isometric force transducers, and stretched to optimal muscle length (L₀). Control responses were obtained at each muscle site with acetylcholine (10–⁸ to 10 ⁴ M), substance P (10–¹¹ to 10^-7 M), or potassium chloride (10 to 80 mM). Muscles were then stimulated with cumulative (10–⁹ to 10–⁶ M) doses of cisapride in the absence or presence of tetrodotoxin (10–⁶ M) and atropine (10–⁶ M), or in a 0 calcium HEPES buffer solution. In cats with idiopathic megacolon, cisapride stimulated contractions of longitudinal smooth muscle from both the ascending and the descending colon. Cisapride-induced contractions were similar in magnitude to those induced by substance P and acetylcholine in the ascending colon, but were less than those observed in the descending colon. Cisapride-induced contractions in megacolonic smooth muscle were only partially inhibited by tetrodotoxin and atropine, but were virtually abolished by removal of extracellular calcium. We concluded that cisapride-induced contractions of feline megacolonic smooth muscle are largely smooth muscle mediated and dependent on influx of extracellular calcium. Cisapride-induced contractions in megacolonic smooth muscle are only partially dependent on enteric cholinergic nerves. Thus, cisapride may be useful in the treatment of cats with idiopathic megacolon.     

Assessment of smooth muscle function in Sesbania drummondii toxicosis in Gallus domesticus

An in vitro assessment based on tissue responsiveness to 2 agonists-histamine and carbachol-was made on smooth muscle activity in chickens experimentally poisoned with sesbania. Crude extracts of Sesbania drummondii were prepared and 2 dosage levels, 0.25% and 0.5% of body weight, were used. The birds were dosed orally with the extract for 3 consecutive days, and on the 4th day segments of ileum and lung were collected from each bird. The isometric contractions of each tissue, produced by the addition of histamine or carbachol in graded concentrations, were recorded. The cumulative concentration-effect curves for the tissues to the agonists were constructed and compared with respective control curves. The results indicated the responsiveness of the tissues in the treated groups was significantly decreased, compared with that of tissues in the controls. Responses of both intestinal and parenchymal strips in the chickens given the higher dosage (0.5%) were decreased significantly, whereas in those given the smaller dosage (0.25%), only parenchyma had a significant response. This indicates that the activity of smooth muscles in general was depressed by sesbania. The effect was more evident in the lung than in the intestine. Therefore, an active principle in the extract which affects smooth muscle, rather than causing direct irritation, may exist. This assessment of smooth muscle activity is sensitive and was effective in detecting changes in tissues from sesbania-treated birds which had not shown any clinical signs. The results also support the possibility that smooth muscle involvement could be a primary cause of toxicity in sesbania poisoning.     

Expression of the ether-a-go-go (ERG) potassium channel in smooth muscle of the equine gastrointestinal tract and influence on activity of jejunal smooth muscle

OBJECTIVE: To determine whether ether-a-go-go (ERG) potassium channels are expressed in equine gastrointestinal smooth muscle, whether ERG channel antagonists affect jejunal muscle contraction in vitro, and whether plasma cisapride concentrations in horses administered treatment for postoperative ileus (POI) are consistent with ERG channels as drug targets. SAMPLE POPULATION: Samples of intestinal smooth muscle obtained from 8 horses free of gastrointestinal tract disease and plasma samples obtained from 3 horses administered cisapride for treatment of POI. PROCEDURE: Membranes were prepared from the seromuscular layer of the duodenum, jejunum, ileum, cecum, large colon, and small colon. Immunoblotting was used to identify the ERG channel protein. Isolated jejunal muscle strips were used for isometric stress response to ERG channel blockers that included E-4031, MK-499, clofilium, and cisapride. Plasma concentrations of cisapride were determined in 3 horses administered cisapride for treatment of POI after small intestinal surgery. RESULTS: Immunoblotting identified ERG protein in all analyzed segments of the intestinal tract in all horses. The selective ERG antagonist E-4031 caused a concentration-dependent increase in jejunal contraction. Clofilium, MK-499, and cisapride also increased jejunal contraction at concentrations consistent with ERG channel block; effects of E-4031 and cisapride were not additive. Peak plasma cisapride concentrations in treated horses were consistent with ERG block as a mechanism of drug action. CONCLUSIONS AND CLINICAL RELEVANCE: The ERG potassium channels modulate motility of intestinal muscles in horses and may be a target for drugs. This finding may influence development of new prokinetic agents and impact treatment of horses with POI.     

Acetylcholine-induced contractions in the porcine internal mammary artery: possible role of muscarinic receptors

The effect of acetylcholine on the isolated, non-precontracted, porcine internal mammary artery (IMA) was investigated. Acetylcholine induced concentration-dependent contractions of non-precontracted IMA rings with denuded endothelium (pEC50 = 5.80 +/- 0.04) and was without effect on arterial segments with intact endothelium. The muscarinic receptor antagonists atropine, pirenzepine, methoctramine and p-fluoro-hexahydro-sila-diphenidol (pFHHSiD) antagonized the response to acetylcholine. The constrained pA2 values were 10.14, 7.74, 7.34 and 10.5, respectively. It is concluded that acetylcholine induces concentration-dependent contractions of porcine internal mammary artery rings on basal tone and that this contractile effect is probably due to direct cholinergic stimulation of smooth muscle cells, maybe including activation of muscarinic M1 receptors.     

Short chain fatty acids stimulate feline colonic smooth muscle contraction

The effect of short chain fatty acids (SCFA) on feline colonic smooth muscle contraction was evaluated in vitro. Colonic tissue was obtained from seven healthy male and female adult cats and seven healthy male and female kittens. Longitudinal and circular colonic smooth muscle strips from proximal and distal colon were incubated with SCFA (acetate, butyrate and propionate; 1-100mM). SCFA-induced contractions were compared to responses obtained using maximal concentrations (10(-4)M) of acetylcholine (ACh). The calcium dependence of the SCFA response was investigated by incubating with nifedipine (1 microM) or verapamil (1 microM). Acetate, butyrate and propionate elicited isometric stress responses (0.25-1.98 x 10(4)N/m(2)) in longitudinal, but not circular, smooth muscle from both the proximal and distal colon of adult cats. Maximal responses were attained at 50 and 100mM SCFA. Maximal butyrate and propionate responses were 29 and 19% of the maximal ACh response (10(-4)M), respectively. Acetate was least effective in stimulating contractile responses. Nifedipine and verapamil abolished all responses. Contractile responses in kittens were similar to those observed in adult cats, but were smaller in amplitude.Results of these studies have shown that SCFA stimulate longitudinal colonic smooth muscle contractions in kittens and adult cats in vitro. These SCFA-induced contractions involve activation of calcium influx. These in vitro findings may account for some of the effects of dietary fiber on feline colonic motility in vivo.     

Characterization of the in vitro responses of equine cecal longitudinal smooth muscle to endothelin-1

OBJECTIVE: To characterize the in vitro response of equine cecal longitudinal smooth muscle (CLSM) to endothelin (ET)-1 and assess the role of ETA and ETB receptors in those ET-1-induced responses. ANIMALS: 36 horses without gastrointestinal tract disease. PROCEDURE: To determine cumulative concentration-response relationships, CLSM strips were suspended in tissue baths containing graded concentrations of ET-1 (10(-9) to 10(-6)M) with or without BQ-123 (ETA receptor antagonist); with or without IRL-1038 (ETB receptor antagonist); or with both antagonists at concentrations of 10(-9), 10(-7), and 10(-5)M. To determine the percentage change in baseline tension of CLSM, the areas under the curve during the 3-minute periods before and after addition of each dose were compared. Also, the effects of ET-1 and a combination of selective ETA and ETB receptor antagonists on electrically evoked contractions were studied. RESULTS: ET-1 caused sustained increases in CLSM tension in a concentration-dependent manner. Contractile responses to ET-1 were not significantly inhibited by either BQ-123 or IRL-1038 alone at any concentration; however, responses were significantly inhibited by exposure to the antagonists together at a concentration of 10(-5)M. Electrical field stimulation did not change the spontaneous contractile activity of CLSM and did not significantly alter the tissue response to ET-1, BQ-123, or IRL-1038. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that ET-1 has a contractile effect on equine CLSM that is mediated via ETA and ETB receptors. In vitro spontaneous contractions of equine CLSM apparently originate in the smooth muscle and not the enteric nervous system.     

Relaxant effects of theophylline and clenbuterol on tracheal smooth muscle from horse and rat in vitro

A comparison between the relaxant effects of clenbuterol and theophylline on horse tracheal smooth muscle has been made in vitro. Rat tracheal smooth muscle was also investigated as a reference. The tracheal preparations were initially contracted with carbachol since the smooth muscle did not spontaneously develop tone. The response of the carbachol-contracted preparations to theophylline was the same in the two species. The response to clenbuterol varied. In only five out of eleven horses were the tracheal smooth muscles sensitive to clenbuterol (mean pD2 = 7.92 M). In the remaining six horses the tracheal smooth muscles were insensitive to clenbuterol (mean pD2 = 3.59 M), yet the preparations responded well to theophylline with complete relaxation. All rat tracheal preparations were insensitive to clenbuterol.     

Distribution of the neurokinin-1 receptor in equine intestinal smooth muscle

REASON FOR PERFORMING STUDY: Tachykinins have profound effects on equine intestinal motility, but the distribution of the neurokinin receptors (NKRs) through which they act is unknown. This study reports the distribution of one of these receptors, the neurokinin-1 receptor (NK1R), in smooth muscle throughout the equine intestinal tract. OBJECTIVES: To quantify the distribution of the NK1R, based upon mRNA expression, in smooth muscle of different regions of the equine intestinal tract. METHODS: Nine regions of the intestinal tract were sampled in 5 mature horses. Total RNA was isolated from smooth muscle and reverse transcribed; NK1R mRNA was then quantified using real-time PCR. RESULTS: NK1R mRNA was found at all levels of the sampled intestinal tract. The smooth muscle of the proximal small intestine and the ventral colon exhibited the highest level of NK1R mRNA expression in the equine intestinal tract. CONCLUSIONS: Tachykinins probably affect intestinal contractility and propulsion in the proximal small intestine and in the ventral colon.     

Prokinetic effects of cisapride, naloxone and parasympathetic stimulation at the equine ileo-caeco-colonic junction

The electromyogram of the terminal ileum, the caecum and the proximal right ventral colon was recorded in fasted conscious ponies receiving intravenously equiactive doses of pilocarpine (0.05 mg/kg) and carbachol (0.01 mg/kg) as acetylcholine analogues; cisapride (0.1 mg/kg) and metoclopramide (2 mg/kg) facilitating acetylcholine release from myenteric neurones and naloxone (0.05 mg/kg) as an antagonist of the endogenous inhibitory opioid system. Both cisapride and naloxone induced typical migrating spike bursts in the colon associated with contractions of caecal body and caecal base. Both pilocarpine and carbachol stimulated the terminal ileum but had opposite effects on the activity of the caeco-colonic segment which was decreased by pilocarpine and increased by carbachol. High doses of metoclopramide had weak and unspecific stimulatory motor effects. It is concluded that a true prokinetic effect at the equine ileo-caeco-colonic junction requires a motor profile which includes coordination between contractions sequentially involving the body and the base of the caecum and migrating spike bursts on the proximal colon. Such changes in the motor profile were produced by cisapride and naloxone and to a lesser extent by carbachol.     

In vitro effects of oxytocin,acepromazine, detomidine,xylazine, butorphanol,terbutaline, isoproterenol,and dantrolene on smooth and skeletal muscles of the equine esophagus

OBJECTIVE: To characterize the in vitro effects of oxytocin, acepromazine, xylazine, butorphanol, detomidine, dantrolene, isoproterenol, and terbutaline on skeletal and smooth muscle from the equine esophagus. ANIMALS: 14 adult horses without digestive tract disease. PROCEDURE: Circular and longitudinal strips from the skeletal and smooth muscle of the esophagus were suspended in tissue baths, connected to force-displacement transducers interfaced with a physiograph, and electrical field stimulation was applied. Cumulative concentration-response curves were generated for oxytocin, acepromazine, xylazine, detomidine, butorphanol, isoproterenol, terbutaline, and dantrolene. Mean maximum twitch amplitude for 3 contractions/min was recorded and compared with predrug-vehicle values for the skeletal muscle segments, and area under the curve (AUC) for 3 contractions/min was compared with predrug-vehicle values for the smooth muscle segments. RESULTS: No drugs caused a significant change in skeletal muscle response. In smooth muscle, isoproterenol, terbutaline, and oxytocin significantly reduced AUC in a concentration-dependent manner. Maximum reduction in AUC was 69% at 10(-4) M for isoproterenol, 63% at 10(-6) M for terbutaline, and 64% at 10(-4) M for oxytocin. CONCLUSIONS AND CLINICAL RELEVANCE: Isoproterenol, terbutaline, and oxytocin cause relaxation of the smooth muscle portion of the esophagus. The clinical relaxant effects on the proximal portion of the esophagus reported of drugs such as oxytocin, detomidine, and acepromazine may be the result of centrally mediated mechanisms.     

The teniae of the equine intestinal tract.

At several locations along the equine cecum and colon, the outer longitudinal portion of the tunica muscularis is gathered into discrete bands of smooth muscle and connective tissue called "teniae". In this study, the disposition of the teniae ceci and coli was traced along the equine intestinal tract. It was discovered that, in several instances, arrays of teniae converge toward the valves and sphincters which separate the various intestinal compartments. The teniae may also provide support for and directionality to, peristaltic contraction waves. The tissue proportions of the teniae vary in different locations. The tenia libera lateralis of the ventral colon is rich in elastic connective tissue, while that of the right dorsal colon is primarily composed of smooth muscle. This may reflect the different responsibilities of these two compartments. The teniae are innervated and their smooth muscle cells are joined by many gap junctions. The connective tissue constituents afford intestinal support while yielding to intestinal distension. The smooth muscle and neural elements may foster active tenial participation in peristalsis. This premise must be tested by electrophysiological experimentation. Further experimentation is also necessary to ascertain whether injury to the teniae might predispose a horse to colic.     

Spontaneous in vitro contractile activity of specimens from the abomasal wall of healthy cows and comparison among dairy breeds

OBJECTIVE: To characterize and compare in vitro contractility patterns of sections of abomasal wall harvested from cattle of 3 dairy breeds. SAMPLE POPULATION: Longitudinal and circular smooth muscle preparations harvested from the antrum and body of the abomasum of 30 recently slaughtered Holstein-Friesian, Brown Swiss, and Simmental X Red Holstein cows. PROCEDURE: Spontaneous isometric contractions of specimens in tissue baths of modified Krebs solution were recorded during a 4-hour period. Maximal amplitude, frequency of contractions, and change of basal tension were used to characterize contractility. Statistical analyses were used to test for differences among time periods, among breeds, between specimen locations, and between fiber orientations. RESULTS: Myoactivity patterns of abomasal smooth muscle preparations are highly variable and differ on the basis of location and fiber orientation. Frequency of contractions differed significantly among time periods for longitudinally oriented specimens with decreasing frequencies of contractions over time. Maximal amplitude of the longitudinally oriented specimens from the antrum increased significantly, whereas maximal amplitude of the circularly oriented specimens from the antrum decreased significantly. Values did not differ significantly among breeds. CONCLUSIONS AND CLINICAL RELEVANCE: Patterns of spontaneous contractility of abomasal wall specimens are not homogeneous. During a 4-hour recording period, maximal amplitude and frequency of contractions of specimens varied significantly with respect to orientation and location; however, spontaneous contractile myoactivity did not differ significantly among breeds. Therefore, breed predisposition for displaced abomasum is not correlated with spontaneous activity of smooth muscle specimens.     

The role of thromboxane A2 in regulating porcine basilar arterial tone

The aim of the present study was to clarify the participation of endogenous arachidonic acid (AA) metabolites in regulating porcine basilar, coronary, pulmonary and mesenteric arterial tones in vitro . A cyclooxygenase inhibitor, indomethacin, relaxed basilar artery but not other arteries examined. Quinacrine (a phospholipase A₂ inhibitor), OKY-046 (a thromboxane (TX) A₂ synthetase inhibitor) and ONO-3708 (a TXA₂/prostaglandin H₂ receptor antagonist) produced relaxation in basilar arteries with intact endothelium. Nordihydroguaiaretic acid (a lipoxygenase inhibitor) had no effect on the tone. The amount of TXB₂ (a stable metabolite of TXA₂) spontaneously released from porcine basilar arteries was 6–10 fold more than those from other arteries. Indomethacin and OKY-046 mostly inhibited the production of TXB₂. Endothelial denudation decreased indomethacin-induced relaxation and the amount of TXB₂. These results suggest that a vasoconstricting substance(s) is released from endothelial cells and possibly smooth muscle cells in porcine basilar arteries in vitro . The main constricting substance is proposed to be TXA₂. On the other hand, several arteries from peripheral vascular beds did not release this vasoconstricting substance.     

乌梅散提取物对兔离体小肠平滑肌运动的影响及机制研究

本研究旨在探究乌梅散提取物对兔离体小肠平滑肌收缩的作用及其机制。取乌梅30 g、柿蒂50 g、诃子12 g、黄连12 g、郁金12 g,通过煎熬制备乌梅散水提取物储液。兔小肠离体后恒温灌流,利用RM6240多道生物信号采集处理系统进行信息采集和记录。观察乌梅散提取物对离体小肠自发收缩的影响,应用乙酰胆碱（Ach）致使兔小肠平滑肌痉挛性收缩,观察中浓度乌梅散提取物（2.18 g/L）对Ach诱导的收缩的影响,并观察其对Ach引起的离体小肠细胞内Ca²⁺和胞外Ca²⁺收缩的影响。试验结果表明,在药物浓度大于1.09 g/L时,可显著抑制兔离体小肠平滑肌自发收缩的振幅和频率（P<0.05）;Ach可极显著诱导小肠平滑肌收缩的振幅（P<0.01）;2.18 g/L乌梅散提取物可极显著抑制Ach引起的痉挛性收缩振幅和频率（P<0.01）;在无Ca²⁺台氏液中,乌梅散提取物可极显著抑制Ach引起的离体小肠细胞内Ca²⁺和胞外Ca²⁺收缩振幅及频率（P<0.01）。综上所述,乌梅散提取物剂量依赖性地抑制小肠平滑肌自发收缩,可抑制小肠痉挛性收缩,其机制可能与抑制细胞内Ca²⁺释放和胞外Ca²⁺内流有关。