Muscle Strips Of Rats Research Articles

Age-dependent effects of the β3 adrenoceptor agonist CL316,243 on human and rat detrusor muscle strips

Motility of detrusor smooth muscle includes adrenergic relaxation and cholinergic contraction. Since the latter may be deregulated in overactive bladder (OAB) pathophysiology, anticholinergics are the standard therapy but occasionally less tolerated due to side effects such as dry mouth and constipation. β3 adrenoceptor agonists also alleviate OAB symptoms by relaxing the detrusor muscle. Their age dependence, however, is far from understood. To address this issue, we induced contractions with KCl (60 mM) and carbachol (from 10 nM to 100 μM) in the presence of the β3 adrenoceptor agonist CL316,243 (from 0.1 to 10 μM) in both human and rat muscle strips. Our results confirmed that both contractions were attenuated by β3 adrenoceptor activation in both species, but with differing age dependence. In humans, specimens from mid-life subjects showed a significantly more pronounced effect of CL316,243 in attenuating carbachol-induced contractions than those from aged subjects (Cohen’s d of maximal attenuation: 1.82 in mid-life versus 0.13 in aged) without altering EC50. Conversely, attenuation of KCl responses by CL316,243 increased during ageing (Spearman correlation coefficient = -0.584, P<0.01). In rats, both KCl- and carbachol-induced contractions were significantly more attenuated by CL316,243 in samples from adolescent as compared to aged samples. Immunohistochemistry in human detrusor sections proved β3 adrenoreceptor abundance to remain unaltered during ageing. In conclusion, our findings suggest differential age-dependent changes in human β3 adrenoceptor-dependent attenuation of detrusor contraction in terms of electromechanical versus pharmacomechanical coupling; they may help understand the differential responsiveness of OAB patients to β3 agents.

Effect of artemether on the mechanical activities of isolated smooth muscles of non-pregnant uterus and ileum in mice and wistar rats

This study investigated the effect of artemether on smooth muscle contractility to drugs in non-pregnant female wistar rats. The effect of artemether (2.1x10-6 to 2.1x10-2) on isolated uterine and ileum muscle strips was studied using sixteen (16) mature female Wister rats (160 -190g) mounted on organ baths. The study further investigated the effect of artemether on sub-acute histopathological examination of the ileum using standard in vivo procedures in mice models. Data obtained from the study were represented on table, graph and photomicrographs. The results of this study revealed that artemether (2.1x10-6 to 2.1x10-2 ) alone did not produce contractile responses, but caused significant inhibition on contractile responses induced by acetylcholine ( 4x10-5 to 4x10- 1M) on isolated ileal smooth muscle tissue in rats in a dose dependent manner (p<0.05); also artemether significantly inhibited the contractions induced by oxytocin 8x10-10 to 1x10-6 I.U.) and barium chloride ( 8x10-6 to 8x10-2 mg/ml ) on uterine smooth muscle strips in rats in a dose dependent manner; with Emax of 13.5 ± 0.2 and 12.6 ±. 0.4 mm respectively, all the observed results were independent of tissue species variation. (p<0.05- 0.01). This study revealed that artemether exhibited no adverse effect on the non-pregnant uterus and the rat ileum, hence its safety in the treatment of malaria, as recommended by the World Health Organization.

Activation of KCNQ channels located on the skeletal muscle membrane by retigabine and its influence on the maximal muscle force in rat muscle strips.

Retigabine is a new antiepileptic drug with the main mechanism of action: activation of voltage-gated potassium channels (Kv7) represented in many tissues including the excitable cells-neuronal and muscular. The aim of this article is to determine the role of potassium channels located on the skeletal muscle membrane in the in vivo and in vitro reduction of muscle contractile activity induced by retigabine. We studied the effects of retigabine on the motor function in vivo using a bar holding test and exploratory activity using open field test in rats. Electrical field stimulation (EFS) was applied to skeletal muscle strips in vitro in order to evaluate muscular activity. We registered a significant decrease in the muscle tone and exploratory activity of rats, treated orally with 60mg/kg bw retigabine. In vitro experiments showed decrease in the maximal muscle force of strips in the presence of retigabine in the medium after both indirect (nerve-like) and direct (muscle-like) stimulation. The effects were fully antagonized by XE-991 (Kv7 channel blocker), which supports our hypothesis about the relation between these types of potassium channels and the observed change in the muscle force. Based on these results, we can conclude that skeletal muscle Kv7 channels play a significant role in the myorelaxation and reduced muscle force registered after treatment with Kv7 channels openers (e.g., retigabine). The hyperpolarization of skeletal muscle membrane caused by accelerated K(+) efflux may be the underlying cause for the effect of retigabine on the muscle tone.

Effect of Aurantii Fructus Immaturus Flavonoid on the Contraction of Isolated Gastric Smooth Muscle Strips in Rats.

This study was designed to investigate the effect of Aurantii fructus immaturus flavonoid (AFIF) on the contraction of isolated gastric smooth muscle in rats and explore its underlying mechanisms. Isolated antral longitudinal smooth muscle strip (ALSMS) and pyloric circular smooth muscle strip (PCSMS) of rats were suspended in tissue chambers. The responses of ALSMS and PCSMS to administration of AFIF were observed. Cyclic guanosine monophosphate (cGMP) and protein kinase G (PKG) levels of PCSMS were measured by ELISA kits. In this study, AFIF showed no significant effect on ALSMS contraction, but it dose-dependently reduced the mean contraction amplitude of PCSMS. When the concentration of AFIF reached 3000 μg/mL, 6000 μg/mL, and 10000 μg/mL, its inhibitory effect on PCSMS contraction was significant. This effect of AFIF was weakened in Ca2+-rich environment. And Nω-nitro-L-arginine methyl (L-NAME), the inhibitor of nitric oxide synthase (NOS), significantly inhibited AFIF's action in comparison with control (P < 0.05). After incubation with AFIF for 30 min, levels of cGMP and PKG in PCSMS were significantly increased compared with control (P < 0.05). Our results suggest that AFIF has a dose-dependent diastolic effect on PCSMS in rats, which may be related to the regulatory pathway of NO/cGMP/PKG/Ca2+.

Receptor-isoform-selective insulin analogues give tissue-preferential effects

The relative expression patterns of the two IR (insulin receptor) isoforms, +/- exon 11 (IR-B/IR-A respectively), are tissue-dependent. Therefore we have developed insulin analogues with different binding affinities for the two isoforms to test whether tissue-preferential biological effects can be attained. In rats and mice, IR-B is the most prominent isoform in the liver (> 95%) and fat (> 90%), whereas in muscles IR-A is the dominant isoform (> 95%). As a consequence, the insulin analogue INS-A, which has a higher relative affinity for human IR-A, had a higher relative potency [compared with HI (human insulin)] for glycogen synthesis in rat muscle strips (26%) than for glycogen accumulation in rat hepatocytes (5%) and for lipogenesis in rat adipocytes (4%). In contrast, the INS-B analogue, which has an increased affinity for human IR-B, had higher relative potencies (compared with HI) for inducing glycogen accumulation (75%) and lipogenesis (130%) than for affecting muscle (45%). For the same blood-glucose-lowering effect upon acute intravenous dosing of mice, INS-B gave a significantly higher degree of IR phosphorylation in liver than HI. These in vitro and in vivo results indicate that insulin analogues with IR-isoform-preferential binding affinity are able to elicit tissue-selective biological responses, depending on IR-A/IR-B expression.

Effect of areca on contraction of colonic muscle strips in rats.

To investigate the effects of areca on the contractile activity of isolated colonic muscle strips in rats and mechanism involved. Each strip (LMPC, longitudinal muscle of proximal colon; CMPC, circular muscle of proximal colon; LMDC, longitudinal muscle of distal colon; CMDC, circular muscle of distal colon.) was suspended in a tissue chamber containing 5 mL Krebs solution (37 degrees C), bubbled continuously with 950 mL.L(-1) O(2) and 50 mL.L(-1) CO(2). The mean contractile amplitude (A), the resting tension (T), and the contractile frequency (F) were simultaneously recorded on recorders. Areca dose dependently increased the mean contractile amplitude, the resting tension of proximal and distal colonic smooth muscle strips in rats (P<0.05). It also partly increased the contractile frequency of colonic smooth muscle strips in rats (P<0.05). The effects were partly inhibited by atropine (the resting tension of LMPC decreased from 0.44 +/- 0.12 to 0.17 +/- 0.03; the resting tension of LMDC decreased from 0.71 +/- 0.14 to 0.03 +/- 0.01; the mean contractile amplitude of LMPC increased from -45.8 +/- 7.2 to -30.5 +/- 2.9; the motility index of CMDC decreased from 86.6 +/- 17.3 to 32.8 +/- 9.3; P<0.05 vs areca), but the effects were not inhibited by hexamethonium (P>0.05). Areca stimulated the motility of isolated colonic smooth muscle strips in rats. The stimulation of areca might be relevant with M receptor partly.

Effects of Dangshen on isolated gastric muscle strips in rats.

AIM:To study the effects of Dangshen dried root of Codonopsis Pilosula (Franch) Nannf on contractile activity of isolated gastric muscle strips in rats and its possible mechanism involved.METHODS:Each isolated gastric muscle strip was put in a tissue chamber containing 5ml Krebs solution, constantly warmed by water jacket at 37?mgr; and supplied with a mixed gas of 95% O(2) and 5% CO(2). After incubating for 1h with 1g tension, Dangshen of varied concentration was added cumulatively in the tissue chamber at intervals of 2 minutes. The isometrical response was measured on ink-writing recorders.RESULTS:Dangshen dose dependence increased the resting tension of longitudinal muscle (LM) of fundus (r =0.96, P < 0.01), the mean contractile amplitude of circular muscle (CM) of the stomach body (r =0.87, P < 0.05) and CM of antrum (r =0.98, P < 0.01), and the motility index CM of pylorus(r =0.87, P < 0.05). Atropine (5 10( 8)mol/L) or Hexamethonium (10( 5)mol/L) or Indomethacin (5 10( 7)mol/L) was given 2 minutes before the administration of Dangshen, it did not abolish its dose related manner. Atropine apparently reduced the increasing action of 10% and 30% Dangshen on the resting tesion of LM of fundus (P < 0.05), 30%, 100% and 200% Dangshen on bodied strips (P < 0.05), 100% and 200% Dangshen on antral strips (P < 0.05).Hexamethonium reduced the increasing action of 10% and 30% Dangshen on the resting tesion of LM of fundus (P < 0.05 and P < 0.05), 30%, 100% and 200% Dangshen on bodied strips (P < 0.05), and 100% and 200% Dangshen on pyloric strips (P < 0.05). Indomethacin inhibited the effect of 10% Dangshen on the resting tesion of LM of fundus (P < 0.05), but did not affect the exciting action of Dangshen on strips of body, antrum and pylorus.CONCLUSION:The results showed that Dangshen possessed exciting action on the isolated gastric smooth muscle strips of the rat.The exciting action of Dangshen was partially mediated via cholinergic M and N receptors.

Glucagon-like peptide-1 retards gastric emptying and small bowel transit in the rat: effect mediated through central or enteric nervous mechanisms.

This study investigated effects of glucagon-like peptide-1(7-36)amide (GLP-1) on gastric emptying, small intestinal transit, and contractility of smooth muscle strips in rats. GLP-1 at doses of 10 and 20 pmol/kg/min administered intravenously dose-dependently retarded transit of the small intestine (P < 0.001), while only the higher dose of 20 pmol/kg/min retarded gastric emptying (P < 0.01). GLP-1 at concentrations up to 10(-4) M did not affect the basal tone or contractility of the gastrointestinal muscle strips that were stimulated with electric field stimulation or acetylcholine. Our results demonstrate that small intestinal transit seems more sensitive than gastric emptying to inhibition by GLP-1 at physiologic levels in plasma. Furthermore, this inhibition appears to be mediated through central mechanisms rather than through peripheral actions. Thus, GLP-1 is suggested to inhibit gastric emptying and small intestinal transit through an indirect effect via central or enteric nervous mechanisms.

Increased responsiveness of jejunal longitudinal muscle in Trichinella-infected rats.

We examined in vitro changes in contractility of jejunal longitudinal muscle strips in rats infected with the nematode parasite Trichinella spiralis. Length-passive tension relationships were unchanged. However, muscle from infected rats on days 5 and 6 postinfection (PI) generated maximal active tension induced by carbachol at significantly less stretch (39.9 +/- 1.0 and 34.3 +/- 6.3%, respectively) than control tissues (66.0 +/- 2.3%). In infected rats on day 5 PI, the maximum tension generated by carbachol (1.6 +/- 0.4 g/mm2) and by 5-hydroxytryptamine (5-HTP) (2.6 +/- 0.1 g/mm2) was significantly greater than in control tissue (0.5 +/- 0.2 g/mm2). On removal of calcium from the medium, responses of muscle from control and infected rats were reduced in a proportionate manner. The increased responsiveness to carbachol and 5-HTP was maximal by day 5 PI and was associated with a decrease in the ED50 value for 5-HTP but not for carbachol. All changes were reversed by 23 days PI. These results indicate that T. spiralis infection in the rat is associated with alterations in jejunal longitudinal smooth muscle function.