Asthmatic airways are stiffer than normal. We have shown that the cytoskeletal passive stiffness of airway smooth muscle (ASM) can be regulated by intracellular signaling pathways, especially those associated with Rho kinase (ROCK). We have also shown that an oscillatory strain reduces the passive stiffness of ASM and its ability to generate force. Here, we investigated the combined effect of inhibiting the ASM contraction with β2 agonist and decreasing the ASM cytoskeletal stiffness with ROCK inhibitor and/or force oscillation (FO) on the relaxation of contracted ASM. We hypothesize that the ASM relaxation can be synergistically enhanced by the combination of these interventions, because drug-induced softening of the cytoskeleton enhances the FO-induced relaxation and vice versa. Sheep tracheal strips were isotonically contracted to acetylcholine (3 × 10-5 M). At the plateau of shortening, β2 agonist salbutamol (10-7 M), ROCK inhibitor H1152 (10-7 M), and FO (square wave, 1 Hz, amplitude 6% maximal active force) were applied either alone or in combination. After adjusting for nonspecific time-dependent variation, relengthening by individual interventions with low-dose salbutamol or H1152, or small amplitude FO was not significantly different from zero. However, significant relengthening was observed in all combination treatments. The relengthening was greater than the mathematical sum of relengthening caused by individual treatments thereby demonstrating synergistic relaxation. The ASM stiffness did not change with salbutamol or H1152 treatments, but was lower with FO in combination with H1152. The results suggest that the mechanopharmacological treatment can be an effective therapy for asthma.

Sarcolipin (SLN) inhibits sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA) pumps. To evaluate the physiological significance of SLN in skeletal muscle, we compared muscle contractility and SERCA activity between Sln-null and wild-type mice. SLN protein expression in wild-type mice was abundant in soleus and red gastrocnemius (RG), low in extensor digitorum longus (EDL), and absent from white gastrocnemius (WG). SERCA activity rates were increased in soleus and RG, but not in EDL or WG, from Sln-null muscles, compared with wild type. No differences were seen between wild-type and Sln-null EDL muscles in force-frequency curves or maximum rates of force development (+dF/dt). Maximum relaxation rates (-dF/dt) of EDL were higher in Sln-null than wild type across a range of submaximal stimulation frequencies, but not during a twitch or peak tetanic contraction. For soleus, no differences were seen between wild type and Sln-null in peak tetanic force or +dF/dt; however, force-frequency curves showed that peak force during a twitch and 10-Hz contraction was lower in Sln-null. Changes in the soleus force-frequency curve corresponded with faster rates of force relaxation at nearly all stimulation frequencies in Sln-null compared with wild type. Repeated tetanic stimulation of soleus caused increased (-dF/dt) in wild type, but not in Sln-null. No compensatory responses were detected in analysis of other Ca(2+) regulatory proteins using Western blotting and immunohistochemistry or myosin heavy chain expression using immunofluorescence. These results show that 1) SLN regulates Ca(2+)-ATPase activity thereby regulating contractile kinetics in at least some skeletal muscles, 2) the functional significance of SLN is graded to the endogenous SLN expression level, and 3) SLN inhibitory effects on SERCA function are relieved in response to repeated contractions thus enhancing relaxation rates.

Research suggests that multiple forms of relaxation training (e.g., progressive muscle relaxation, meditation, breathing exercises, visualization, and autogenics) can help individuals reduce stress, enhance relaxation states, and improve overall well-being. We examined three different, commonly used approaches to stress relaxation-progressive muscle relaxation, deep breathing, and guided imagery-and evaluated them in a head-to-head comparison against each other and a control condition. Sixty healthy undergraduate participants were randomized to one of the four conditions and completed 20 minutes of progressive muscle relaxation, deep breathing, or guided imagery training that was delivered by recorded audio instruction. Baseline and follow-up assessment of psychological relaxation states were completed. Physiological relaxation was also assessed continuously using measures of electrodermal activity and heart rate. Results showed that progressive muscle relaxation, deep breathing, and guided imagery all increased the state of relaxation for participants in those groups, compared to participants in the control group. In each case, the increase was statistically significant and although the groups did not differ on relaxation before training, all groups were significantly higher on relaxation after training, as compared to the control group. Progressive muscle relaxation and guided imagery showed an immediate linear trend toward physiological relaxation, compared to the control group, and the deep breathing group showed an immediate increase in physiological arousal followed quickly by a return to initial levels. Our results lend support to the body of research showing that stress relaxation training can be effective in improving relaxation states at both the psychological and physiological level. Future research could examine stress relaxation techniques in a similar manner using designs where multiple techniques can be compared in the same samples.

1. Electrophysiological and mechanical experiments were performed to investigate whether the nitric oxide (NO)-mediated relaxation of rabbit urethral smooth muscle is associated with a hyperpolarization of the membrane potential. In addition, a possible role for vasoactive intestinal peptide (VIP) and carbon monoxide (CO) as relaxant agents in rabbit urethra was investigated. 2. Immunohistochemical experiments were performed to characterize the NO-synthase (NOS) and VIP innervation. Possible target cells for NO were studied by using antisera against cyclic GMP. The cyclic GMP-immunoreactivity was investigated on tissues pretreated with 1 mM IBMX, 0.1 mM zaprinast and 1 mM sodium nitroprusside. 3. Intracellular recordings of the membrane potential in the circular smooth muscle layer revealed two types of spontaneous depolarizations, slow waves with a duration of 3-4 s and an amplitude of 30-40 mV, and faster (0.5-1 s), more irregular depolarizations with an amplitude of 5-15 mV. The resting membrane potential was 39 +/- 1 mV (n = 12). Application of NO (30 microM), CO (30 microM) or VIP (1 microM) did not change the resting membrane potential. 4. Both NO (1-100 microM) and VIP (1 nM-1 microM) produced concentration-dependent relaxations amounting to 87 +/- 4% and 97 +/- 2% (n = 6), respectively. The relaxant effect of CO (1-30 microM) amounted to 27 +/- 4% (n = 5) at the highest concentration used. 5. Immunohistochemical experiments revealed a rich supply of NOS-immunoreactive nerve fibres in the smooth muscle layers. Numerous spinous cyclic GMP-immunoreactive cells were found interspersed between the smooth muscle bundles, mainly localized in the outer layer. These cells had long processes forming a network surrounding the smooth muscle bundles. VIP-immunoreactivity was sparse in comparison to NOS-immunoreactive nerves. 6. The rich supply of NOS-immunoreactive nerve fibres supports the view that NO is an important NANC-mediator in the rabbit urethra. In contrast to several other tissues, the relaxant effect of NO in the rabbit urethra does not seem to be mediated by hyperpolarization. The network of cyclic GMP-immunoreactive cells may constitute target cells for NO, but their function remains to be established.

1. A contracting muscle resists stretching with a force greater than the force it can exert at a constant length, T(o). If the muscle is kept active at the stretched length, the excess tension disappears, at first rapidly and then more slowly (stress relaxation). The present study is concerned with the first, fast tension decay. In particular, it is still debated if and to what extent the fast tension decay after a ramp stretch involves a conservation of the elastic energy stored during stretching into cross-bridge states of higher chemical energy. 2. Single muscle fibres of Rana temporaria and Rana esculenta were subjected to a short ramp stretch (approximately 15 nm per half-sarcomere at either 1.4 or 0.04 sarcomere lengths s(-1)) on the plateau of the force-length relation at temperatures of 4 and 14 degrees C. Immediately after the end of the stretch, or after discrete time intervals of fixed-end contraction and stress relaxation at the stretched length (Delta t(isom) = 0.5-300 ms), the fibre was released against a force ~T(o). Fibre and sarcomere stiffness during the elastic recoil to T(o) (phase 1) and the subsequent transient shortening against T(o) (phase 2), which is expression of the work enhancement by stretch, were measured after different Delta t(isom) and compared with the corresponding fast tension decay during Delta t(isom). 3. The amplitude of fast tension decay is large after the fast stretch, and small or nil after the slow stretch. Two exponential terms are necessary to fit the fast tension decay after the fast stretch at 4 degrees C, whereas one is sufficient in the other cases. The rate constant of the dominant exponential term (0.1-0.2 ms(-1) at 4 degrees C) increases with temperature with a temperature coefficient (Q(10)) of approximately 3. 4. After fast stretch, the fast tension decay during Delta t(isom) is accompanied in both species and at both temperatures by a corresponding increase in the amplitude of phase 2 shortening against T(o) after Delta t(isom): a maximum of approximately 5 nm per half-sarcomere is attained when the fast tension decay is almost complete, i.e. 30 ms after the stretch at 4 degrees C and 10 ms after the stretch at 14 degrees C. After slow stretch, when fast tension decay is small or nil, the increase in phase 2 shortening is negligible. 5. The increase in phase 2 work during fast tension decay (Delta W(out)) is a constant fraction of the elastic energy simultaneously set free by the recoil of the undamped elastic elements. 6. Delta W(out) is accompanied by a decrease in stiffness, indicating that it is not due to a greater number of cross-bridges. 7. It is concluded that, during the fast tension decay following a fast ramp stretch, a transfer of energy occurs from the undamped elastic elements to damped elements within the sarcomeres by a temperature-dependent mechanism with a dominant rate constant consistent with the theory proposed by A. F. Huxley and R. M. Simmons in 1971.

Sleep is critical for health, cognition, and restorative processes, and yet, many experience chronic sleep restriction. Sleep interventions have been designed to enhance overnight sleep quality and physiology. Components of these interventions, like relaxation-based progressive muscle relaxation (PMR), have been studied in isolation and have shown direct effects on sleep architecture, including increasing time in restorative, slow-wave sleep (SWS). These relaxation methods have been understudied in naps, which are effective fatigue countermeasures that reduce deleterious effects of chronic sleep restriction. We hypothesised that PMR should boost SWS in a nap, as compared to an active control. We used a between-subject design in which healthy young adults underwent PMR training or listened to Mozart music (control) prior to a 90-min nap opportunity. We assessed changes in the amount and lateralisation of SWS, as evidence suggests left hemispheric lateralisation may be a proxy for recuperative sleep needs, and changes to state-dependent anxiety and fatigue before and after the nap to assess intervention success. We found PMR participants spent ~10 min more in SWS, equivalent to 125% more time, than the control group, and concomitantly, significantly less time in rapid eye movement sleep. PMR participants also had greater right lateralised slow-wave activity and delta activity compared to the control suggesting a more well-rested brain profile during sleep. Further, pre-sleep anxiety levels predicted nap architecture in the intervention group, suggesting benefits may be impacted by anxiety. The feasibility and accessibility of PMR prior to a nap make this an interesting research avenue to pursue with strong translational application.

Stretch-induced relaxation has not been clearly identified in gastrointestinal tract. The present study is to explore the role of large conductance calcium-activated potassium channels (BKCa) in stretch-induced relaxation of colon. The expression and currents of BKCa were detected and the basal muscle tone and contraction amplitude of colonic smooth muscle strips were measured. The expression of BKCa in colon is higher than other GI segments (P < 0.05). The density of BKCa currents was very high in colonic smooth muscle cells (SMCs). BKCa in rat colonic SMCs were sensitive to stretch. The relaxation response of colonic SM strips to stretch was attenuated by charybdotoxin (ChTX), a nonspecific BKCa blocker (P < 0.05). After blocking enteric nervous activities by tetrodotoxin (TTX), the stretch-induced relaxation did not change (P > 0.05). Still, ChTX and iberiotoxin (IbTX, a specific BKCa blocker) attenuated the relaxation of the colonic muscle strips enduring stretch (P < 0.05). These results suggest stretch-activation of BKCa in SMCs was involved in the stretch-induced relaxation of colon. Our study highlights the role of mechanosensitive ion channels in SMCs in colon motility regulation and their physiological and pathophysiological significance is worth further study.

cGMP-dependent kinase I (cGKI) is a major mediator of smooth muscle relaxation and exists in two isoforms, α and β. Both isoforms are supposed to mediate their effects via different intracellular signaling pathways. To verify this concept, the kinetics of relaxation mediated by either isoform was analyzed in gastric fundus smooth muscle from mice. Muscles from mice that express selectively the Iα or Iβ isoform of cGKI in smooth muscle (sm-cGKIα or sm-cGKIβ mice) were compared to muscles from conventional cGKI(-/-) mice. Fundus muscles were contracted by carbachol and then relaxed by 8-Br-cGMP or by electrical field stimulation (EFS). The time course of relaxation by 8-Br-cGMP was not different between muscles from sm-cGKIα and sm-cGKIβ mice. EFS induced a fast transient relaxation in muscles from sm-cGKIα and sm-cGKIβ mice that was blocked by the NO synthase inhibitor L-NAME. Recovery from this relaxation was about 4-times slower in muscles from sm-cGKIα mice than in muscles from sm-cGKIβ mice. The different kinetic of recovery from relaxation after EFS in sm-cGKIα and sm-cGKIβ mice suggests that different signaling pathways exist for each cGKI isoform in vivo in fundus muscles.

1. The effects of adenosine triphosphate (ATP), adenosine diphosphate (ADP), alpha,beta-methylene-ATP (alpha,beta-MeATP) and 2-methylthio-ATP (2-MeSATP) on longitudinally orientated smooth muscle strips from marmoset urinary bladder were investigated by use of standard organ bath techniques. 2. After being mounted in superfusion organ baths, 66.7% (n=249) of marmoset detrusor smooth muscle strips developed spontaneous tone, 48.2% of all strips examined developed tone equivalent to greater than 0.1 g mg(-1) of tissue and were subsequently utilized in the present investigation. 3. On exposure to ATP, muscle strips exhibited a biphasic response, a rapid and transient contraction followed by a more prolonged relaxation. Both responses were found to be concentration-dependent. ADP and 2-MeSATP elicited a similar response (contraction followed by relaxation), whereas application of alpha,beta-MeATP only produced a contraction. The potency order for each effect was alpha,beta-MeATP> >2-MeSATP> ATP>ADP (contractile response) and ATP=2-MeSATP> or = ADP> > alpha,beta-MeATP (relaxational response). 4. Desensitization with alpha,beta-MeATP (10 microM) abolished the contractile phase of the response to ATP, but had no effect on the level of relaxation evoked by this agonist. On the other hand, the G-protein inactivator, GDPbetaS (100 microM) abolished only the relaxation response to ATP. Suramin (general P2 antagonist, 100 microM) shifted both the contractile and relaxation ATP concentration-response curves to the right, whereas cibacron blue (P2Y antagonist, 10 microM) only antagonized the relaxation response to ATP. In contrast, the adenosine receptor antagonist, 8-phenyltheophylline (10 microM), had no effect on the relaxation response curve to ATP. 5. Incubation with tetrodotoxin (TTX, 3 microM) or depolarization of the muscle strip with 40 mM K+ Krebs failed to abolish the relaxation to ATP. In addition, neither Nomega-nitro-L-arginine (L-NOARG, 10 microM) nor methylene blue (10 microM) had any effect on the relaxation response curve. However, tos-phe-chloromethylketone (TPCK, 3 microM), an inhibitor of cyclicAMP-dependent protein kinase A (PKA), significantly (P<0.01) shifted the curve for the ATP-induced relaxation to the right. 6. It is proposed that marmoset detrusor smooth muscle contains two receptors for ATP, a classical P2X-type receptor mediating smooth muscle contraction, and a P2Y (G-protein linked) receptor mediating smooth muscle relaxation. The results also indicate that the ATP-evoked relaxation may occur through the activation of cyclicAMP-dependent PKA.

Transcranial magnetic stimulation (TMS) of the motor cortex can be used during a voluntary contraction to inhibit corticospinal drive to the muscle and consequently induce involuntary muscle relaxation. Our aim was to evaluate the reproducibility and the effect of varying experimental conditions (robustness) of TMS-induced muscle relaxation. Relaxation of deep finger flexors was assessed in 10 healthy subjects (5 M, 5 F) using handgrip dynamometry with normalized peak relaxation rate as main outcome measure, that is, peak relaxation rate divided by (voluntary plus TMS-evoked)force prior to relaxation. Both interday and interrater reliability of relaxation rate were high with intraclass correlation coefficient of 0.88 and 0.92 and coefficient of variation of 3.8 and 3.7%, respectively. Target forces of 37.5% of maximal voluntary force or higher resulted in similar relaxation rate. From 50% of maximal stimulator output and higher relaxation rate remained the same. Only the most lateral position (>2 cm from the vertex) rendered lower relaxation rate (mean ± SD: 11.1 ± 3.0 s-1 , 95% CI: 9.0-13.3 s-1 ) compared to stimulation at the vertex (12.8 ± 1.89 s-1 , 95% CI: 11.6-14.1 s-1 ). Within the range of baseline skin temperatures, an average change of 0.5 ± 0.2 s-1 in normalized peak relaxation rate was measured per 1°C change in skin temperature. In conclusion, interday and interrater reproducibility and reliability of TMS-induced muscle relaxation of the finger flexors were high. Furthermore, this technique is robust with limited effect of target force, stimulation intensity, and coil position. Muscle relaxation is strongly affected by skin temperature; however, this effect is marginal within the normal skin temperature range. We deem this technique well suited for clinical and scientific assessment of muscle relaxation.

Nitrovasodilators and agonists, via an increase in intracellular cyclic nucleotide levels, can induce smooth muscle relaxation without a concomitant decrease in phosphorylation of the regulatory light chains (RLC) of myosin. However, since cyclic nucleotide-induced relaxation is associated with a decrease in intracellular [Ca(2+)], and hence, a decreased activity of MLCK, we tested the hypothesis that the site responsible for the elevated RLC phosphorylation is not Ser19. Smooth muscle strips from gastric fundus were isometrically contracted with ET-1 which induced an increase in monophosphorylation from 9 ± 1 % under resting conditions (PSS) to 36 ± 1 % determined with 2D-PAGE. Electric field stimulation induced a rapid, largely NO-mediated relaxation with a half time of 8 s, which was associated with an initial decline in RLC phosphorylation to 18 % within 2 s and a rebound to 34 % after 30 s whereas relaxation was sustained. In contrast, phosphorylation of RLC at Ser19 probed with phosphospecific antibodies declined in parallel with force. LC/MS and western blot analysis with phosphospecific antibodies against monophosphorylated Thr18 indicate that Thr18 is significantly monophosphorylated during sustained relaxation. We therefore suggest that (i) monophosphorylation of Thr18 rather than Ser19 is responsible for the phosphorylation rebound during sustained EFS-induced relaxation of mouse gastric fundus, and (ii) that relaxation can be ascribed to dephosphorylation of Ser19, the site considered to be responsible for regulation of smooth muscle tone.

Diastolic dysfunction refers to an impaired relaxation and an abnormality in a heart's filling during diastole while left ventricular systolic function is preserved. Diastolic dysfunction is commonly observed in patients with primary hypertension, diabetes and cardiomyopathies such as hypertrophic cardiomyopathy or restrictive cardiomyopathy. We have generated a restrictive cardiomyopathy (RCM) mouse model with troponin mutations in the heart to mimic the human RCM patients carrying the same mutations.

We explored the effects of progressive muscle relaxation (PMR) on anxiety, depression, and quality of life (QOL) in patients with pulmonary arterial hypertension (PAH). One hundred and thirty Han Chinese patients with PAH were randomly assigned to a PMR group (n = 65) and a control group (n = 65). In a 12-week study duration, the PMR group received hospital-based group and in-home PMR practice, while the control group received hospital-based mild group stretching and balance exercises. The control group and the PMR group were comparable at baseline. After 12 weeks of intervention, the PMR group showed significant improvement in anxiety, depression, overall QOL, and the mental component summary score of QOL (P < 0.05) but not the physical component summary score of QOL or the 6-minute walking distance. In contrast, the control group showed no significant improvement in any of the variables. Moreover, the PMR group showed significant improvement in all QOL mental health domains (P < 0.05) but not the physical health domains. In contrast, the control group showed no significant improvement in any QOL domain. In conclusion, this study suggests that PMR practice is effective in improving anxiety, depression, and the mental health components of QOL in patients with PAH.

The pharmacological properties of nitroxyl (HNO) donors in the gastrointestinal tract are unknown. We investigated the properties of this molecule in the regulation of gastrointestinal contractility focusing on its possible interaction with other gaseous signaling molecules such as NO and H2S. Organ bath, Ca2+ imaging, and microelectrode recordings were performed on rat intestinal samples, using Angeli's salt as HNO donor. Angeli's salt caused a concentration-dependent relaxation of longitudinal or circular muscle strips of the ileum and the proximal colon. This relaxation was strongly inhibited by the Rho-kinase inhibitor Y-27632 (10 μM), by the reducing agent DTT or by the inhibitor of soluble guanylate cyclase (sGC) ODQ (10 μM) alone or in combination with the inhibitors of the endogenous synthesis of H2S β-cyano-L-alanine (5 mM) and amino-oxyacetate (5 mM). Preventing endogenous synthesis of NO by the NO synthase inhibitor L-NAME (200 μM) did not affect the relaxation induced by HNO. HNO induced an increase in cytosolic Ca2+ concentration in colonic myocytes. It also elicited myocyte membrane hyperpolarization that amounted to -10.6 ± 1.1 mV. ODQ (10 μM) and Apamin (1 μM), a selective inhibitor of small conductance Ca2+-activated K+ channels (SKca), strongly antagonized this effect. We conclude that HNO relaxes the gastrointestinal tract musculature by hyperpolarizing myocytes via activation of the sGC/cGMP pathway similarly to NO, not only inhibiting the RhoK and activating MLCP as do both NO and H2S but also increasing cytosolic Ca2+ for activation of SK C a contributing to hyperpolarization.

Enhanced airway smooth muscle (ASM) contraction is an important component in the pathophysiology of asthma. We have shown that ligand gated chloride channels modulate ASM contractile tone during the maintenance phase of an induced contraction, however the role of chloride flux in depolarization-induced contraction remains incompletely understood. To better understand the role of chloride flux under these conditions, muscle force (human ASM, guinea pig ASM), peripheral small airway luminal area (rat ASM) and airway smooth muscle plasma membrane electrical potentials (human cultured ASM) were measured. We found ex vivo guinea pig airway rings, human ASM strips and small peripheral airways in rat lungs slices relaxed in response to niflumic acid following depolarization-induced contraction induced by K(+) channel blockade with tetraethylammonium chloride (TEA). In isolated human airway smooth muscle cells TEA induce depolarization as measured by a fluorescent indicator or whole cell patch clamp and this depolarization was reversed by niflumic acid. These findings demonstrate that ASM depolarization induced contraction is dependent on chloride channel activity. Targeting of chloride channels may be a novel approach to relax hypercontractile airway smooth muscle in bronchoconstrictive disorders.

Ginsenoside, an extract of Panax ginseng, is an essential constituent of anti-asthmatic Chinese herbal medicine. To elucidate whether ginsenoside affects airway smooth muscle tone and, if so, what the mechanism of action is, we studied relaxant responses of human bronchial strips under isometric condition in vitro, and directly measured the release of nitric oxide (NO) by an amperometric sensor for this molecule. Addition of ginsenoside relaxed the tissues precontracted with acetylcholine in a dose-dependent manner, the maximal relaxation and the ginsenoside concentration required to produce 50% relaxation being 67+/-8% and 210+/-29 microg ml(-1), respectively. The relaxant responses to ginsenoside were inhibited by N(G)-nitro-L-arginine methylester (L-NAME) and removal of the epithelium, but not by N(G)-nitro-D-arginine methylester (D-NAME) or tetrodotoxin. This inhibitory effect of L-NAME was reversed by L-arginine but not by D-arginine. Addition of ginsenoside to the medium containing bronchial tissues dose-dependently increased NO-selective electrical current, and this effect was greatly attenuated by the epithelial removal or Ca(2+)-free medium. Ginsenoside also increased tissue cyclic GMP contents, an effect that was abolished in the presence of L-NAME. It is concluded that ginsenoside induces relaxation of human bronchial smooth muscle via stimulation of NO generation predominantly from airway epithelium and cyclic GMP synthesis. This action might account for the anti-asthmatic effect of Panax ginseng.

Plasma pH can be altered during pregnancy and at labor. Membrane excitability of smooth muscle including uterine muscle is suppressed by the activation of K(+) channels. Because contractility of uterine muscle is regulated by extracellular pH and humoral factors, K(+) conductance could be connected to factors regulating uterine contractility during pregnancy. Here, we showed that TASK-2 inhibitors such as quinidine, lidocaine, and extracellular acidosis produced contraction in uterine circular muscle of mouse. Furthermore, contractility was significantly increased in pregnant uterine circular muscle than that of non-pregnant muscle. These patterns were not changed even in the presence of tetraetylammonium (TEA) and 4-aminopyridine (4-AP). Finally, TASK-2 inhibitors induced strong myometrial contraction even in the presence of L-methionine, a known inhibitor of stretchactivated channels in myometrium. When compared to non-pregnant myometrium, pregnant myometrium showed increased immunohistochemical expression of TASK-2. Therefore, TASK-2, seems to play a key role during regulation of myometrial contractility in the pregnancy and provides new insight into preventing preterm delivery.

The mechanism(s) of action responsible for the beneficial effects of phosphodiesterase 5 (PDE5) inhibitors including sildenafil on lower urinary tract symptoms suggestive of benign prostate hyperplasia are unclear. In particular, the role of the NO-cGMP signalling pathway in regulating human bladder dome smooth muscle relaxation is questionable. Thus, we assessed the ability of a PDE5 inhibitor, sildenafil, to relax such tissue, and identified the signalling pathways involved in this relaxation.

In order to characterize the β-adrenoceptor (AR) subtypes involved in agonist-stimulated relaxation of murine urinary bladder we studied the effects of (-)-isoprenaline and CL 316,243 on tonic contraction and spontaneous contractions in detrusor strips of wild-type (WT) and β2-AR knockout (β2-AR KO) mice.

The dose of neuromuscular blocking drugs is commonly based on body weight, but using muscle mass might be more effective. This study investigated the relationship between the effect of neuromuscular blocking drugs and muscle mass measured using bioelectrical impedance analysis.