Muscle Contraction In Rats Research Articles

Does the capsaicin-sensitive local neural circuit constitutively regulate vagally evoked esophageal striated muscle contraction in rats?

To determine whether a capsaicin-sensitive local neural circuit constitutively modulates vagal neuromuscular transmission in the esophageal striated muscle or whether the neural circuit operates in a stimulus-dependent manner, we compared the motility of esophageal preparations isolated from intact rats with those in which capsaicin-sensitive neurons had been destroyed. Electrical stimulation of the vagus nerve trunk evoked contractile responses in the esophagus isolated from a capsaicin-treated rat in a manner similar to those in the esophagus from a control rat. No obvious differences were observed in the inhibitory effects of D-tubocurarine on intact and capsaicin-treated rat esophageal motility. Destruction of the capsaicin-sensitive neurons did not significantly affect latency, time to peak and duration of a vagally evoked twitch-like contraction. These findings indicate that the capsaicin-sensitive neural circuit does not operate constitutively but rather is activated in response to an applied stimulus.

Effects of Chronic Tenotomy on the Post-Tetanic Responses of Fast and Slow Muscles in Rats

The effects of tenotomy present for two weeks on the post-tetanic responses of isolated fast (extensor digitorum longus) and slow (soleus) muscles were studied by isometric recording of muscle contraction in rats. After tetanic stimulation with bursts of 100 impulses at a frequency of 20 impulses/sec, the force of single fast muscle contractions exceeded the pretetanic level by 20‐25% (p < 0.05) in both intact and tenotomized muscles. In similar conditions, the slow muscle soleus showed a decrease in the amplitudes of single contractions, i.e., post-tetanic depression. Post-tetanic depression was not seen after tenotomy. Caffeine (4 mM) increased the force of single and tetanic contractions in control and tenotomized fast muscles, though no corresponding increase in post-tetanic responses were seen. In slow muscles, caffeine had no effect on the nature of post-tetanic responses. Dantrolene (10 μM) decreased the force of single and tetanic contractions but did not prevent the appearance of post-tetanic potentiation in fast muscles and depression in intact slow muscles. The fact that the phenomenon of post-tetanic potentiation disappeared after denervation of fast muscles within two weeks while it was present after tenotomy for as long as 40 days after surgery provides grounds for suggesting the existence of a potentiating factor which reaches muscles by axonal transport and increases single contractions.

Postnatal changes in vagal control of esophageal muscle contractions in rats

AimsReplacement of smooth muscles by striated muscles occurs in the esophagus during the early postnatal period. The aim of this study was to clarify postnatal changes in vagal control of esophageal muscle contractions in rats. Main methodsAn isolated segment of the neonatal rat esophagus was placed in an organ bath and the contractile responses were recorded using a force transducer. Key findingsElectrical stimulation of the vagus trunk evoked a biphasic contractile response in the neonatal esophageal segment. The first and second components of the contractions were inhibited by α-bungarotoxin and atropine, respectively. Ganglion blockers, hexamethonium and mecamylamine, did not affect vagally mediated contractions. The first component gradually enlarged with age in days, whereas the second component declined during the first week after birth. Application of d-tubocurarine or acetylcholine caused an apparent contraction in the esophageal striated muscle at postnatal day 0, but responses to these drugs were not observed at 1week after birth. The neonatal esophagus expressed the γ-subunit of nicotinic acetylcholine receptors. In contrast, the ε-subunit was dominantly expressed in the adult esophagus. SignificanceThe vagus nerves directly innervate both the esophageal striated muscles and smooth muscles in the early neonatal period. During the process of muscle rearrangement, the property of the striated muscles is altered substantially. The specific features of striated muscles in the neonatal rat esophagus might compensate for immature formation of neuromuscular junctions. Unsuccessful conversion of the striated muscle property during postnatal muscle rearrangement would be related to disorders of esophageal motility.

Nerve growth factor contributes augmented P2X3 expression of primary afferent neurons by femoral occlusion

Femoral artery occlusion augments the reflex sympathetic nerve and pressor responses to muscle metabolites and to muscle contraction in rats. Also, P2X3 receptors contribute the metabolic component of the exercise pressor reflex. Thus, the purpose of this study was to examine if femoral occlusion alters expression of P2X3 in dorsal root ganglion (DRG) neurons and its responsiveness in rats. In addition, we examined role of nerve growth factor (NGF) in the levels of P2X3 proteins in sensory neurons. Our western blot results showed that 24hrs of femoral ligation increased the levels of P2X3 (optical density: 0.93±0.07 in control vs. 1.37±0.10 after occlusion, P<0.05). The fluorescence immunohistochemistry further demonstrated that the occlusion elevated P2X3 expression in DRG neurons (percentage of P2X3 positive cells: 33±3% in control vs.51±3% in occlusion, P<0.05). Furthermore, our results showed that responses of renal sympathetic nerve activity and blood pressure to stimulation of P2X were greater in occluded rats than in control rats by injection of α,β me-ATP into the arterial blood supply of hindlimb muscle. Finally, infusion of NGF in the hindlimb muscles of healthy rats increased P2X3 (optical density: 0.98±0.12 in control vs. 1.37±0.16 with NGF, P<0.05). Our findings suggest that the levels of P2X3 in primary afferent neurons are increased as the blood supply to the hindlimb is insufficient, and NGF is likely responsible for enhanced P2X3. (Supported by NIH R01 HL-090720, P01HL-096570, and AHA grant 0840130N).

Turning the PAGe on central control of the exercise pressor reflex in humans

experiments in biological science are often envisioned as ultimately providing rational approaches to problems confronting human health. Additionally, pragmatic solutions evoked by clinical problems often provoke new questions in basic science. Deep brain stimulation therapy in human patients with

Bradykinin receptor blockade reduces sympathetic nerve response to muscle contraction in rats with ischemic heart failure

Previous animal and human studies have suggested that a muscle reflex engaged during contraction leads to heightened levels of sympathetic activity in congestive heart failure (CHF). The present experiment was designed to test the role for bradykinin, which is produced within contracting skeletal muscle and contributes to the muscle reflex through its action on kinin B(2) receptors located on the endings of thin fiber muscle afferents. CHF was induced in rats by myocardial infarction (MI) after coronary artery ligation. Echocardiography was performed to determine fractional shortening (FS), an index of the left ventricular function. In the decerebrate rats, we examined renal sympathetic nerve activity (RSNA) during 1 min intermittent (1 to 4 s stimulation to relaxation) contraction of left triceps surae muscles. RSNA responded synchronously as tension was developed, and the response was significantly (P < 0.05) greater in MI rats [+39 +/- 9% s(-1) (integrated RSNA over time); n = 16] with 20 +/- 2% of FS than that in control healthy rats (+19 +/- 2% s(-1); n = 16) with 49 +/- 2% of FS. Tension development did not differ significantly between the two groups of rats. Thirty minutes after intra-arterial injection into the hindlimb circulation of the kinin B(2) receptor antagonist, HOE-140 (2 microg/kg), the RSNA response to contraction was significantly reduced in the MI rats (+26 +/- 7% s(-1)) but not in the control rats (+17 +/- 2% s(-1)). These data suggest that bradykinin within contracting muscle is part of the exaggerated muscle reflex seen in CHF.

Local hindlimb antioxidant infusion does not affect muscle glucose uptake during in situ contractions in rat

There is evidence that reactive oxygen species (ROS) contribute to the regulation of skeletal muscle glucose uptake during highly fatiguing ex vivo contraction conditions via AMP-activated protein kinase (AMPK). In this study we investigated the role of ROS in the regulation of glucose uptake and AMPK signaling during low-moderate intensity in situ hindlimb muscle contractions in rats, which is a more physiological protocol and preparation. Male hooded Wistar rats were anesthetized, and then N-acetylcysteine (NAC) was infused into the epigastric artery (125 mg.kg(-1).h(-1)) of one hindlimb (contracted leg) for 15 min before this leg was electrically stimulated (0.1-ms impulse at 2 Hz and 35 V) to contract at a low-moderate intensity for 15 min. The contralateral leg did not receive stimulation or local NAC infusion (rest leg). NAC infusion increased (P<0.05) plasma cysteine and cystine (by approximately 360- and 1.4-fold, respectively) and muscle cysteine (by 1.5-fold, P=0.001). Although contraction did not significantly alter muscle tyrosine nitration, reduced (GSH) or oxidized glutathione (GSSG) content, S-glutathionylation of protein bands at approximately 250 and 150 kDa was increased (P<0.05) approximately 1.7-fold by contraction, and this increase was prevented by NAC. Contraction increased (P<0.05) skeletal muscle glucose uptake 20-fold, AMPK phosphorylation 6-fold, ACCbeta phosphorylation 10-fold, and p38 MAPK phosphorylation 60-fold, and the muscle fatigued by approximately 30% during contraction and NAC infusion had no significant effect on any of these responses. This was despite NAC preventing increases in S-glutathionylation with contraction. In conclusion, unlike during highly fatiguing ex vivo contractions, local NAC infusion during in situ low-moderate intensity hindlimb contractions in rats, a more physiological preparation, does not attenuate increases in skeletal muscle glucose uptake or AMPK signaling.

Effects of autonomic nerve stimulation on colorectal motility in rats

Several disease processes of the colon and rectum, including constipation and incontinence, have been associated with abnormalities of the autonomic nervous system. However, the autonomic innervation to the colon and rectum are not fully understood. The aims of this study were to investigate the effect of stimulation of vagus nerves, pelvic nerves (PN) and hypogastric nerves (HGN) on colorectal motility in rats. Four strain gauge transducers were implanted on the proximal colon, mid colon, distal colon and rectum to record circular muscle contractions in rats. Electrical stimulation was administered to the efferent distal ends of the cervical vagus nerve, PN and HGN. Motility index (MI) was evaluated before and during stimulation. Electrical stimulation (5-20 Hz) of the cervical vagus elicited significant contractions in the mid colon and distal colon, whereas less pronounced contractions were observed in the proximal colon. Pelvic nerves stimulation elicited significant contractions in the rectum as well as the mid colon and distal colon. Atropine treatment almost completely abolished the contractions induced by vagus nerve and PN stimulation. Hypogastric nerves stimulation caused relaxations in the rectum, mid colon and distal colon. The relaxations in response to HGN stimulation were abolished by propranolol. Vagal innervation extends to the distal colon, while the PN has projections in the distribution of the rectum through the mid colon. This suggests a pattern of dual parasympathetic innervation in the left colon. Parasympathetic fibers regulate colorectal contractions via muscarinic receptors. The HGN mainly regulates colorectal relaxations via beta-adrenoceptors.

Some different effect of PKC inhibitors on the acetylcholine, and endothelin-1-induced contractions of rat bronchial smooth muscle

Although the role of protein kinase C (PKC) has been suggested in agonist-induced bronchial smooth muscle contractions, the PKC isoform(s) involved in the phenomenon are not yet clear now. Moreover, contractile agonists may have different signaling pathways in airway smooth muscle contraction. Therefore, the identification of PKC isoforms playing a role in rat bronchial smooth muscle was investigated. The presence of PKCα, β, γ, δ, ε, η, ζ, λ and ι isoforms was determined by immunoblot in the muscle. The effects of four PKC inhibitors, GF109203X, calphostin C, Gö6976 and rottlerin on acetylcholine and endothelin-1-induced bronchial smooth muscle contractions were then examined. The inhibitors were cumulatively administered after the acetylcholine or endothelin-1-induced contraction reached plateau. Since the acetylcholine-induced bronchial smooth muscle contraction was significantly inhibited by GF109203X (PKCs α, β, γ, δ and ε inhibitor) and calphostin C (conventional and novel PKCs inhibitor) but not by Gö6976 (PKCs α, β and γ inhibitor) and rottlerin (PKCs δ and θ inhibitor), novel PKCs might be involved in the acetylcholine-induced contraction. On the other hand, the bronchial smooth muscle contraction by endothelin-1 was significantly inhibited by GF109203X, calphostin C and Gö6976 but not by rottlerin. The conventional PKC might partially play important role in the endothelin-1 induced contraction. In conclusion, the present study clearly demonstrated the expression of multiple PKC isoforms in rat bronchial smooth muscle. Some different PKC isoforms might be partly involved between the acetylcholine and endothelin-1-induced bronchial smooth muscle contractions in rats.

Receptor Synergy From Thin Fiber Muscle Afferents. Focus on “Dorsal Root Ganglion Neurons Innervating Skeletal Muscle Respond to Physiological Combinations of Protons, ATP, and Lactate Mediated by ASIC, P2X, and TRPV1”

In the recent article by Light et al., the authors identify the substances critical to signaling pain and fatigue in skeletal muscle. The identified substances act on Group III and IV fibers, which are thinly myelinated and unmyelinated, respectively, and correspond to their better known cutaneous

Contraction‐induced fatty acid uptake and oxidation are regulated in part via CaMKKβ‐dependent AMPK activation in perfused rat muscle

Ca2+/calmodulin‐dependent protein kinase kinase (CaMKK) and AMP‐activated protein kinase (AMPK) have been individually implicated in the regulation of muscle substrate metabolism during exercise. The purpose of this study was to determine if CaMKKβ is involved in the regulation of FA metabolism during muscle contraction in rats. Rat hindlimbs were perfused at rest (n=16), with 3mM caffeine (n=15), with 2mM AICAR (n=16), or during moderate intensity muscle contraction (n=14), and with or without 5μM STO‐609, a CaMKKβ inhibitor. FA uptake and oxidation increased (P&lt;0.05) by 83 and 68% with caffeine treatment, 54 and 94% with AICAR treatment and 78 and 126% with muscle contraction. STO‐609 abolished (P&lt;0.05) caffeine‐ and contraction‐induced FA uptake and oxidation, but had no effect with AICAR treatment (P&gt;0.05). CaMKKβ activity was increased (P&lt;0.05) 102% by caffeine treatment and 136% by muscle contraction, but was not affected by AICAR treatment (P&gt;0.05). STO‐609 prevented the caffeine‐ and contraction‐induced increase in CaMKKβ activity. Caffeine, AICAR and muscle contraction increased (P&lt;0.05) AMPKα2 activity by 240%, 12‐fold and 496%, but did not affect (P&gt;0.05) AMPKα1 activity. STO‐609 decreased (P&lt;0.05) AMPKα2 activity by 54 and 52% during caffeine treatment and muscle contraction, but did not affect (P&gt;0.05) AICAR‐induced activity. These results show the critical importance of Ca2+‐dependent signaling via CaMKKβ activation in the regulation of FA uptake and oxidation in contracting rat skeletal muscle.

Probable involvement of epsilon-isoform of protein kinase C in rat bronchial smooth muscle contraction induced by acetylcholine

Although the role of protein kinase C (PKC) has been suggested in agonist-induced bronchial smooth muscle contraction, the PKC isoform(s) involved in this phenomenon is not clear now. In the present study, the effects of three PKC inhibitors, GF1092603X, Gö6976 and rottlerin on acetylcholine (ACh)-induced bronchial smooth muscle contraction were examined to identify the PKC isoform(s) involved in the contraction. Bronchial smooth muscles were pretreated with each PKC inhibitor (10(-6) and 10(-5) M) 30 min before cumulative administration of ACh. In another series of experiments, the effects of PKC inhibitors on the maximal contraction induced by 10(-3) M ACh were determined: the inhibitors were cumulatively administered (10(-8)- 10(-5) M) after the ACh-induced contraction reached plateau. The ACh-induced bronchial smooth muscle contraction was significantly inhibited by GF109203X (inhibitor of PKC alpha, beta, gamma, delta and epsilon) but not by Gö6976 (PKC delta, beta and gamma inhibitor) and rottlerin (PKC delta and theta inhibitor). Moreover, mRNA and protein of PKC epsilon were detected in rat bronchial smooth muscle. Taken together, PKC epsilon might be involved in the ACh-induced bronchial smooth muscle contraction in rats.

Local Nitric Oxide Synthase Inhibition Reduces Skeletal Muscle Glucose Uptake but Not Capillary Blood Flow During In Situ Muscle Contraction in Rats

We have previously shown in humans that local infusion of a nitric oxide synthase (NOS) inhibitor into the femoral artery attenuates the increase in leg glucose uptake during exercise without influencing total leg blood flow. However, rodent studies examining the effect of NOS inhibition on contraction-stimulated skeletal muscle glucose uptake have yielded contradictory results. This study examined the effect of local infusion of an NOS inhibitor on skeletal muscle glucose uptake (2-deoxyglucose) and capillary blood flow (contrast-enhanced ultrasound) during in situ contractions in rats. Male hooded Wistar rats were anesthetized and one hindleg electrically stimulated to contract (2 Hz, 0.1 ms) for 30 min while the other leg rested. After 10 min, the NOS inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) (arterial concentration of 5 micromol/l) or saline was infused into the epigastric artery of the contracting leg. Local NOS inhibition had no effect on blood pressure, heart rate, or muscle contraction force. Contractions increased (P < 0.05) skeletal muscle NOS activity, and this was prevented by L-NAME infusion. NOS inhibition caused a modest significant (P < 0.05) attenuation of the increase in femoral blood flow during contractions, but importantly there was no effect on capillary recruitment. NOS inhibition attenuated (P < 0.05) the increase in contraction-stimulated skeletal muscle glucose uptake by approximately 35%, without affecting AMP-activated protein kinase (AMPK) activation. NOS inhibition attenuated increases in skeletal muscle glucose uptake during contraction without influencing capillary recruitment, suggesting that NO is critical for part of the normal increase in skeletal muscle fiber glucose uptake during contraction.

Fibre‐type specificity of interleukin‐6 gene transcription during muscle contraction in rat: association with calcineurin activity

In this study, we quantified the transcription of the interleukin-6 (IL-6) gene in individual fibres and the associated changes in calcineurin activity assessed at the cellular level during prolonged muscle contraction. Individual myofibres were isolated from plantaris and soleus muscles of rats at the end of an exhaustive running exercise test (n = 10), categorized according to their myosin heavy chain isoform content, and compared to those of resting rats (n = 10). Using real-time PCR analysis in individual fibres, a marked rise in IL-6 transcript levels occurred in type I and IIa fibres at the end of exercise (P < 0.05). Transcription of the gene encoding for the modulatory calcineurin-interacting protein-1 (MCIP-1), a sensitive indicator of calcineurin activity, also mainly increased in type I and IIa fibres (P < 0.05). Moreover, a slight increase in MCIP-1 mRNA levels was observed in type IIx (P < 0.05). Fibre types determined by immunohistochemistry were qualitatively examined for glycogen content using periodic acid-Shiff staining, and no direct relationship was found, at the cellular level, between glycogen content, fibre-type and IL-6 transcription. Our data clearly suggest that IL-6 gene transcription was mainly observed in early recruited myofibres and that contraction-induced IL-6 transcription could be associated with enhanced calcineurin activity.

Mechanisms mediating cholinergic antral circular smooth muscle contraction in rats

To investigate the pathway (s) mediating rat antral circular smooth muscle contractile responses to the cholinomimetic agent, bethanechol and the subtypes of muscarinic receptors mediating the cholinergic contraction. Circular smooth muscle strips from the antrum of Sprague-Dawley rats were mounted in muscle baths in Krebs buffer. Isometric tension was recorded. Cumulative concentration-response curves were obtained for (+)-cis-dioxolane (cD), a nonspecific muscarinic agonist, at 10(-8)-10(-4) mol/L, in the presence of tetrodotoxin (TTX, 10(-7) mol/L). Results were normalized to cross sectional area. A repeat concentration-response curve was obtained after incubation of the muscle for 90 min with antagonists for M1 (pirenzepine), M2 (methoctramine) and M3 (darifenacin) muscarinic receptor subtypes. The sensitivity to PTX was tested by the ip injection of 100 mg/kg of PTX 5 d before the experiment. The antral circular smooth muscles were removed from PTX-treated and non-treated rats as strips and dispersed smooth muscle cells to identify whether PTX-linked pathway mediated the contractility to bethanechol. A dose-dependent contractile response observed with bethanechol, was not affected by TTX. The pretreatment of rats with pertussis toxin decreased the contraction induced by bethanechol. Lack of calcium as well as the presence of the L-type calcium channel blocker, nifedipine, also inhibited the cholinergic contraction, with a reduction in response from 2.5+/-0.4 g/mm2 to 1.2+/-0.4 g/mm(2) (P<0.05). The dose-response curves were shifted to the right by muscarinic antagonists in the following order of affinity: darifenacin (M(3))>methocramine (M(2)) >pirenzepine (M(1)). The muscarinic receptors-dependent contraction of rat antral circular smooth muscles was linked to the signal transduction pathway(s) involving pertussis-toxin sensitive GTP-binding proteins and to extracellular calcium via L-type voltage gated calcium channels. The presence of the residual contractile response after the treatment with nifedipine, suggests that an additional pathway could mediate the cholinergic contraction. The involvement of more than one muscarinic receptor (functionally predominant type 3 over type 2) also suggests more than one pathway mediating the cholinergic contraction in rat antrum.

Cobalt injections into the pedunculopontine nuclei attenuate the reflex diaphragmatic responses to muscle contraction in rats.

Previous studies have suggested that neurons in the pedunculopontine nucleus (PPN) are activated during static muscle contraction. Furthermore, activation of the PPN, via electrical stimulation or chemical disinhibition, is associated with increases in respiratory activity observed via diaphragmatic electromyogram recordings. The present experiments address the potential for PPN involvement in the regulation of the reflex diaphragmatic responses to muscle contraction in chloralose-urethane anesthetized rats. Diaphragmatic responses to unilateral static hindlimb muscle contraction, evoked via electrical stimulation of the tibial nerve, were recorded before and subsequent to bilateral microinjections of a synaptic blockade agent (CoCl2) into the PPN. The peak reflex increases in respiratory frequency (9.0 +/- 1.0 breaths/min) and minute integrated diaphragmatic electromyogram activity (14.6 +/- 3.3 units/min) were attenuated after microinjection of CoCl2 into the PPN (2.6 +/- 0.9 breaths/min and 4.6 +/- 2.1 units/min, respectively). Consistent diaphragmatic responses were observed in the subset of animals that were barodenervated. Control experiments suggest no effects of PPN synaptic blockade on the cardiovascular responses to muscle contraction. The results are discussed in terms of a potential role for the PPN in modulation of the reflex respiratory adjustments that accompany muscular activity.

Increased expression of G12 and G13 proteins in bronchial smooth muscle of airway hyperresponsive rats

To obtain information on the activation pathway of the monomeric G protein, RhoA, in bronchial smooth muscle, the expression of G alpha12 and G alpha13 in bronchial smooth muscle of the rat was determined. The levels of these G proteins were also compared between antigen-induced airway hyperresponsive and normal control groups. Actively sensitized rats were repeatedly challenged by antigen inhalation. Twenty-four hours after the final antigen challenge, membrane preparations of bronchial smooth muscles were prepared. Immunoblottings were performed, and the density ratios of G alpha12/beta-actin and G alpha13/beta-actin were calculated to quantify the levels of these G-protein alpha subunits. Both G alpha12 and G alpha13 proteins were expressed in rat bronchial smooth muscle. The levels of bronchial G alpha12 and G alpha13 proteins in the repeatedly antigen challenged rats were significantly increased as compared with those in control animals; the magnitude of upregulation in the airway-hyperresponsive group was 89% and 68% in the control group, respectively. G alpha12 and G alpha13 proteins were expressed in rat bronchial smooth muscle. Considering the probable involvement of G12 and G13 proteins in Ca2+ sensitization through Rho protein, the augmented expression of such G proteins after repeated antigen challenge may be responsible for the hyperresponsiveness of bronchial smooth muscle contraction in rats.

Microtubules Regulate Pulmonary Vascular Smooth Muscle Contraction

Microtubules are ubiquitous in eukaryotic cells. However, the role of microtubules in the mechanisms of pulmonary vascular smooth contraction has not previously been described. The purpose of this study was to examine the effect of microtubular inhibition (vinblastine) on the following mechanisms of pulmonary vascular smooth muscle contraction in rats using isolated pulmonary artery rings: (1) receptor- independent, calcium-dependent contraction via smooth muscle cell depolarization (response to KCl); (2) receptor-dependent, calcium-dependent contraction via α1-adrenergic receptor stimulation (response to phenylephrine, PE); (3) receptor-dependent, calcium-independent contraction via thromboxane A2receptor stimulation (response to the thromboxane mimetic, U-46619). Rats were studied 4 days after administration of vinblastine (750 μg/kg iv). Concentration–response curves were generated for KCl (5 mMto 100 mM) and for PE and U-46619 (10−9to 10−4M) (n= 8 rings/4 rats per group). Saline injected rats were controls. Pulmonary vascular smooth muscle contraction by calcium-dependent and -independent mechanisms was significantly increased following microtubular inhibition. These findings suggest that microtubules have an important role in the response of pulmonary vascular smooth muscle to vasoconstricting agonists.

Mediation of anaphylaxis-induced jejunal circular smooth muscle contraction in rats

Altered intestinal motility and diarrhea are features of food protein-induced intestinal anaphylaxis in the conscious rat. These experiments were performed to determine the mediator(s) responsible for jejunal circular smooth muscle contraction during this response. Hooded-Lister rats were sensitized by intraperitoneal injection of 10-micrograms egg albumin, and controls were sham-sensitized with saline. Fourteen days later the contractility of the circular muscle in jejunal segments (mucosa intact) was examined in standard tissue baths in response to antigen (Ag) or other agents. While control and sensitized tissues contracted in similar fashion in response to stretch, bethanechol, histamine, or 5-hydroxytryptamine (5HT), Ag contracted only the segments of sensitized animals. The contractile response was: (1) specific to the sensitizing Ag, as bovine serum albumin did not induce contraction and (2) could be passively transferred with serum containing specific immunoglobulin E antibody (IgE-Ab). Concanavalin A, which degranulates both mucosal and connective tissue-type mast cells, and compound 48/80, which degranulates only connective tissue-type mast cells produced contractile responses. Ag-induced contraction was significantly inhibited by the mucosal and connective tissue-type mast cell stabilizer doxantrazole, but not the connective tissue mast cell stabilizer disodium cromoglycate. Diphenhydramine and cimetidine together significantly inhibited histamine-induced contraction, but failed to effect the Ag-induced contraction in sensitized tissues. While the contractile response to 5HT was reduced in the presence of methysergide (5HT1-receptor antagonist), cinanserin (5HT2-receptor antagonist), and ICS 205-930 (5HT3-receptor antagonist), only cinanserin significantly inhibited the contractile response to Ag. Indomethacin significantly inhibited Ag-induced contraction. Ag-induced contraction was resistant to atropine and tetrodotoxin.(ABSTRACT TRUNCATED AT 250 WORDS)

Potentiation and restitution of heart muscle contraction in rats adapted to exercise

The original amplitude of contraction of strips of myocardium determined the inotropic response to paired stimulation. The higher the initial amplitude, the lower the degree of potentiation and the higher the degree of restitution of contraction. For equal amplitude, the degree of potentiation of myocardial contraction of exercise-adapted rats was greater and the degree of restitution smaller than in the control. These changes probably reflect changes in the ion transport system of the myocardial cells.