OBJECTIVE: To study hesperetin-induced vasorelaxation after depolarizing contraction in human umbilical veins (HUVs) to elucidate the role of L-type Ca²⁺ channel (LTCC) and related signaling pathway. METHODS: Isometric tension recording was performed in HUV rings pre-contracted with K⁺. Hesperetin relaxing mechanism was investigated using a LTCC opener (BayK8644) and blockers of cyclic nucleotides and phosphodiesterases (PDEs). Whole-cell patch-clamping in A7r5 cells, a rat vascular smooth muscle cell line, was performed to study the effect of hesperetin on LTCC current. RESULTS: After depolarizing precontraction, hesperetin induced HUV relaxation concentration-dependently and endothelium-independently; 1 mmol/L hesperetin reduced denuded HUV ring tension by 68.7% ± 4.3% compared to matching vehicle, osmolality, and time controls (P<0.0001). Importantly, hesperetin competitively inhibited BayK8644-induced contraction, shifting the half maximal effective concentration of BayK8644 response from 1.08 nmol/L [95% confidence interval (CI) 0.49-2.40] in vehicle control to 11.30 nmol/L (95% CI 5.45-23.41) in hesperetin (P=0.0001). Moreover, hesperetin elicited further vasorelaxation in denuded HUV rings pretreated with inhibitors of soluble guanylyl cyclase, adenylyl cyclase, PDE3, PDE4, and PDE5 (P<0.01), while rings pretreated with PDE1 inhibitors could not be relaxed by hesperetin (P>0.05). However, simultaneously applying inhibitors of soluble guanylyl cyclase and adenylyl cyclase could not inhibit hesperetin's effect (P>0.05). In whole-cell patch-clamping, hesperetin rapidly decreased LTCC current in A7r5 cells to 66.7% ± 5.8% (P=0.0104). CONCLUSIONS Hesperetin diminishes depolarizing contraction of human vascular smooth muscle through inhibition of LTCC, and not cyclic nucleotides nor PDEs. Our evidence supports direct LTCC interaction and provides additional basis for the use of hesperetin and its precursor hesperidin as vasodilators and may lead to future vasodilator drug development as a treatment alternative for cardiovascular diseases.
Hesperidin/pharmacology* ; Humans ; Calcium Channels, L-Type/metabolism* ; Umbilical Veins/physiology* ; Muscle Contraction/drug effects* ; Animals ; Rats ; Calcium Channel Blockers/pharmacology* ; Vasodilation/drug effects* ; Muscle Relaxation/drug effects*

Objective: To investigate the present situation of pelvic floor muscle strength, and to analyze the factors affecting pelvic floor muscle strength. Methods: The data of patients who were admitted into the general outpatient department of gynecology, Peking University People's Hospital from October 2021 to April 2022 were collected, and the patients who met the exclusion criteria were included in this cross sectional study. The patient's age, height, weight, education level, defecation way and defecation time, birth history, maximum newborn birth weight, occupational physical activity, sedentary time, menopause, family history and disease history were recorded by questionnaire. Morphological indexes such as waist circumference, abdomen circumference and hip circumference were measured with tape measure. Handgrip strength level was measured with grip strength instrument. After performing routine gynecological examinations, the pelvic floor muscle strength was evaluated by palpation with modified Oxford grading scale (MOS). MOS grade>3 was taken as normal group and ≤3 as decreased group. Binary logistic regression was used to investigate the related factors of deceased pelvic floor muscle strength. Results: A total of 929 patients were included in the study, and the average MOS grade was 2.8±1.2. By univariate analysis, birth history, menopausal time, defecation time, handgrip strength level, waist circumference and abdominal circumference were related to the decrease of pelvic floor muscle strength (all P<0.05). By binary logistic regression analysis, the level of handgrip strength (OR=0.913, 95%CI: 0.883-0.945; P<0.001) was correlated with normal pelvic floor muscle strength; waist circumference (OR=1.025, 95%CI: 1.005-1.046; P=0.016), birth history (OR=2.224, 95%CI: 1.570-3.149; P<0.001), sedentary time> 8 hours (OR=2.073, 95%CI: 1.198-3.587; P=0.009) were associated with the decrease of pelvic floor muscle strength. Conclusions: The level of handgrip strength is related to the normal pelvic floor muscle strength of females, while the waist circumference, birth history and sedentary time>8 hours are related to the decrease of pelvic floor muscle strength of females. In order to prevent the decrease of pelvic floor muscle strength, it is necessary to carry out relevant health education, enhance exercise, improve the overall strength level, reduce daily sedentary time, maintain symmetry, and carry out comprehensive overall intervention to improve pelvic floor muscle function.
Adult ; Female ; Humans ; Cross-Sectional Studies ; Gynecology ; Hand Strength ; Muscle Contraction/physiology* ; Muscle Strength/physiology* ; Outpatients ; Pelvic Floor/physiology*

OBJECTIVE: To explore the role of endoplasmic reticulum ryanodine receptor 1 (RyR1) expression and phosphorylation in sepsis- induced diaphragm dysfunction. METHODS: Thirty SPF male SD rats were randomized equally into 5 groups, including a sham-operated group, 3 sepsis model groups observed at 6, 12, or 24 h following cecal ligation and perforation (CLP; CLP-6h, CLP-12h, and CLP-24h groups, respectively), and a CLP-24h group with a single intraperitoneal injection of KN- 93 immediately after the operation (CLP-24h+KN-93 group). At the indicated time points, diaphragm samples were collected for measurement of compound muscle action potential (CMAP), fatigue index of the isolated diaphragm and fitted frequencycontraction curves. The protein expression levels of CaMK Ⅱ, RyR1 and P-RyR1 in the diaphragm were detected using Western blotting. RESULTS: In the rat models of sepsis, the amplitude of diaphragm CMAP decreased and its duration increased with time following CLP, and the changes were the most obvious at 24 h and significantly attenuated by KN-93 treatment (P < 0.05). The diaphragm fatigue index increased progressively following CLP (P < 0.05) irrespective of KN- 93 treatment (P>0.05). The frequency-contraction curve of the diaphragm muscle decreased progressively following CLP, and was significantly lower in CLP-24 h group than in CLP-24 h+KN-93 group (P < 0.05). Compared with that in the sham-operated group, RyR1 expression level in the diaphragm was significantly lowered at 24 h (P < 0.05) but not at 6 or 12 following CLP, irrespective of KN-93 treatment; The expression level of P-RyR1 increased gradually with time after CLP, and was significantly lowered by KN-93 treatment at 24 h following CLP (P < 0.05). The expression level of CaMKⅡ increased significantly at 24 h following CLP, and was obviously lowered by KN-93 treatment (P < 0.05). CONCLUSION Sepsis causes diaphragmatic dysfunction by enhancing CaMK Ⅱ expression and RyR1 receptor phosphorylation in the endoplasmic reticulum of the diaphragm.
Rats ; Male ; Animals ; Diaphragm/metabolism* ; Ryanodine Receptor Calcium Release Channel/metabolism* ; Rats, Sprague-Dawley ; Phosphorylation ; Muscle Contraction/physiology* ; Endoplasmic Reticulum ; Sepsis/metabolism*

Lower limb ankle exoskeletons have been used to improve walking efficiency and assist the elderly and patients with motor dysfunction in daily activities or rehabilitation training, while the assistance patterns may influence the wearer's lower limb muscle activities and coordination patterns. In this paper, we aim to evaluate the effects of different ankle exoskeleton assistance patterns on wearer's lower limb muscle activities and coordination patterns. A tethered ankle exoskeleton with nine assistance patterns that combined with differenet actuation timing values and torque magnitude levels was used to assist human walking. Lower limb muscle surface electromyography signals were collected from 7 participants walking on a treadmill at a speed of 1.25 m/s. Results showed that the soleus muscle activities were significantly reduced during assisted walking. In one assistance pattern with peak time in 49% of stride and peak torque at 0.7 N·m/kg, the soleus muscle activity was decreased by (38.5 ± 10.8)%. Compared with actuation timing, the assistance torque magnitude had a more significant influence on soleus muscle activity. In all assistance patterns, the eight lower limb muscle activities could be decomposed to five basic muscle synergies. The muscle synergies changed little under assistance with appropriate actuation timing and torque magnitude. Besides, co-contraction indexs of soleus and tibialis anterior, rectus femoris and semitendinosus under exoskeleton assistance were higher than normal walking. Our results are expected to help to understand how healthy wearers adjust their neuromuscular control mechanisms to adapt to different exoskeleton assistance patterns, and provide reference to select appropriate assistance to improve walking efficiency.
Aged ; Ankle/physiology* ; Ankle Joint/physiology* ; Biomechanical Phenomena/physiology* ; Electromyography ; Exoskeleton Device ; Gait/physiology* ; Humans ; Muscle Contraction ; Muscle, Skeletal/physiology* ; Walking/physiology*

Human motion control system has a high degree of nonlinear characteristics. Through quantitative evaluation of the nonlinear coupling strength between surface electromyogram (sEMG) signals, we can get the functional state of the muscles related to the movement, and then explore the mechanism of human motion control. In this paper, wavelet packet decomposition and : coherence analysis are combined to construct an intermuscular cross-frequency coupling analysis model based on wavelet packet- : coherence. In the elbow flexion and extension state with 30% maximum voluntary contraction force (MVC), sEMG signals of 20 healthy adults were collected. Firstly, the subband components were obtained based on wavelet packet decomposition, and then the : coherence of subband signals was calculated to analyze the coupling characteristics between muscles. The results show that the linear coupling strength (frequency ratio 1:1) of the cooperative and antagonistic pairs is higher than that of the nonlinear coupling (frequency ratio 1:2, 2:1 and 1:3, 3:1) under the elbow flexion motion of 30% MVC; the coupling strength decreases with the increase of frequency ratio for the intermuscular nonlinear coupling, and there is no significant difference between the frequency ratio : and : . The intermuscular coupling in beta and gamma bands is mainly reflected in the linear coupling (1:1), nonlinear coupling of low frequency ratio (1:2, 2:1) between synergetic pair and the linear coupling between antagonistic pairs. The results show that the wavelet packet- : coherence method can qualitatively describe the nonlinear coupling strength between muscles, which provides a theoretical reference for further revealing the mechanism of human motion control and the rehabilitation evaluation of patients with motor dysfunction.
Adult ; Algorithms ; Electromyography ; Humans ; Movement ; Muscle Contraction ; Muscle, Skeletal ; physiology ; Range of Motion, Articular

Penile erectile dysfunction (ED) is ascribed to the contraction-relaxation imbalance of smooth muscle cells (SMC), the weakening of their diastolic function and the strengthening of their systolic function. The contraction-related signaling pathways, cell membrane ion channels and SMC phenotypes all participate in the regulation of their contraction and its malfunction may cause a variety of SMC-related diseases. The signaling pathways RhoA/Rock and Raf/MEK/ERK1/2 interact with each other, suppressing the expression of the RhoA protein or reducing the level of Rock2 phosphorylation, which may contribute to the treatment of ED. The poor performance of VDCC or TRPC is reckoned to be an important cause of hypertension- or diabetes-related ED. The expressions of CaV1.2, TRPC1 and TRPC4 can be upregulated by many pathological factors, which may enhance the contraction of SMCs. The pathogenesis of ED may be associated with the differentiation of the phenotypes corpus cavernosal SMCs. This review focuses on the recent progress in the studies of the relationship between SMC contraction and ED.
Animals ; Diabetes Complications ; etiology ; physiopathology ; Erectile Dysfunction ; etiology ; physiopathology ; Humans ; Hypertension ; complications ; Ion Channels ; metabolism ; Male ; Mitogen-Activated Protein Kinase 3 ; Muscle Contraction ; physiology ; Myocytes, Smooth Muscle ; physiology ; Penile Erection ; physiology ; Phosphorylation ; Signal Transduction ; physiology

BACKGROUND/AIMS: Although bisacodyl is a widely administered laxative, its underlying mechanism of action remains generally unknown. This study focuses on investigating the effects of bisacodyl on the human colon muscle contraction, and elucidating its mechanism of action. METHODS: Sigmoid colon muscle strips (20 longitudinal and 18 circular muscles) were obtained from 20 subjects who underwent colectomy for colon cancer. Isometric force measurements were calculated in response to electrical field stimulation (EFS, 0.3 milliseconds in trains of 10 Hz for 20 seconds, 150 V). Peak and nadir (tone) during and after EFS, were measured in a controlled state, and after sequential addition of bisacodyl (1 μM), atropine (1 μM), N-nitro-L-arginine (L-NNA, 100 μM), MRS2500 (1 μM), and tetrodotoxin (TTX, 1 μM) to the organ bath. RESULTS: Transient phasic contractions were observed during EFS, and after cessation of EFS. In the longitudinal muscles, nadir during EFS, and tone after EFS, significantly increased after addition of bisacodyl, and persisted after sequential addition of atropine, L-NNA, MRS2500, and TTX, indicating a direct action of bisacodyl on the smooth muscle. In the second experiment, pretreatment of TTX abolished EFS-induced phasic contractions. Although no phasic contraction was produced after perfusion of bisacodyl, tone was increased, thereby supporting evidence of a direct mechanism of action of bisacodyl on the colon smooth muscle. CONCLUSIONS: Bisacodyl increases the tone of longitudinal muscle in the human sigmoid colon through a direct action on the smooth muscle. Further study is warranted to investigate the neural mechanism of action of bisacodyl.
Atropine ; Baths ; Bisacodyl ; Colectomy ; Colon ; Colon, Sigmoid ; Colonic Neoplasms ; Humans ; In Vitro Techniques ; Muscle Contraction ; Muscle, Smooth ; Muscles ; Perfusion ; Physiology ; Tetrodotoxin

BACKGROUNDAdenomyosis (AM) has impaired contraction. This study aimed to explore the expression of potassium channels related to contraction in myometrial smooth muscle cells (MSMCs) of AM.

METHODSUterine tissue samples from 22 patients (cases) with histologically confirmed AM and 12 (controls) with cervical intraepithelial neoplasia were collected for both immunohistochemistry and real-time polymerase chain reaction to detect the expression of large conductance calcium- and voltage-sensitive K + channel (BKCa)-α/β subunits, voltage-gated potassium channel (Kv) 4.2, and Kv4.3. Student's t-test was used to compare the expression.

RESULTSThe BKCa-α/β subunits, Kv4.2, and Kv4.3 were located in smooth muscle cells, glandular epithelium, and stromal cells. However, BKCa-β subunit expression in endometrial glands of the controls was weak, and Kv4.3 was almost undetectable in the controls. The expression of BKCa-α messenger RNA (mRNA) (0.62 ± 0.19-fold decrease, P < 0.05) and Kv4.3 mRNA (0.67 ± 0.20-fold decrease, P < 0.05) decreased significantly in the MSMCs of the control group compared with the AM group. However, there were no significant differences in BKCa-β subunit mRNA or Kv4.2 mRNA.

CONCLUSIONSThe BKCa-α mRNA and the Kv4.3 mRNA are expressed significantly higher in AM than those in the control group, that might cause the abnormal uterus smooth muscle contractility, change the microcirculation of uterus to accumulate the inflammatory factors, impair the endometrium further, and aggravate the pain.

Adenomyosis ; metabolism ; Adult ; Female ; Humans ; Immunohistochemistry ; Large-Conductance Calcium-Activated Potassium Channels ; metabolism ; Male ; Myocytes, Smooth Muscle ; metabolism ; Potassium Channels, Voltage-Gated ; metabolism ; Real-Time Polymerase Chain Reaction ; Shal Potassium Channels ; metabolism ; Uterine Contraction ; physiology ; Uterine Neoplasms ; metabolism ; Uterus ; metabolism

PURPOSE: This study investigated the correlation between isometric muscle strength, gross motor function, and gait parameters in patients with spastic cerebral palsy and to find which muscle groups play an important role for gait pattern in a flexed knee gait. MATERIALS AND METHODS: Twenty-four ambulatory patients (mean age, 10.0 years) with spastic cerebral palsy who were scheduled for single event multilevel surgery, including distal hamstring lengthening, were included. Preoperatively, peak isometric muscle strength was measured for the hip flexor, hip extensor, knee flexor, and knee extensor muscle groups using a handheld dynamometer, and three-dimensional (3D) gait analysis and gross motor function measure (GMFM) scoring were also performed. Correlations between peak isometric strength and GMFM, gait kinematics, and gait kinetics were analyzed. RESULTS: Peak isometric muscle strength of all muscle groups was not related to the GMFM score and the gross motor function classification system level. Peak isometric strength of the hip extensor and knee extensor was significantly correlated with the mean pelvic tilt (r=-0.588, p=0.003 and r=-0.436, p=0.033) and maximum pelvic obliquity (r=-0.450, p=0.031 and r=-0.419, p=0.041). There were significant correlations between peak isometric strength of the knee extensor and peak knee extensor moment in early stance (r=0.467, p=0.021) and in terminal stance (r=0.416, p=0.043). CONCLUSION: There is no correlation between muscle strength and gross motor function. However, this study showed that muscle strength, especially of the extensor muscle group of the hip and knee joints, might play a critical role in gait by stabilizing pelvic motion and decreasing energy consumption in a flexed knee gait.
Biomechanical Phenomena ; Cerebral Palsy/*physiopathology/surgery ; Female ; Gait/*physiology ; Humans ; Isometric Contraction/physiology ; Knee/physiopathology ; Knee Joint/surgery ; Male ; Muscle Spasticity/etiology/physiopathology ; Muscle Strength/*physiology ; Muscle Strength Dynamometer ; Muscle, Skeletal/*physiopathology ; Pelvis ; Postural Balance/physiology ; Tenotomy

OBJECTIVETo observe the effect of β₃adrenoceptors (β₃-AR) activation on rat thoracic aorta smooth muscle contractility and the possible related mechanism.

METHODSThe endothelium removed thoracic aorta was pre-contracted with 30 mmol/L KCl physiological saline solution (PSS). Then the tension of the thoracic aorta was recorded in presence of BRL37344 (BRL) to determine the action of β₃-AR. The tension of the thoracic aorta was also recorded in the presence of Propranolol (PRA), SR59230A (SR), L-NNA, H-89 and Iberiotoxin (IBTX) respectively to reveal the underling mechanism of β₃-AR activation on rat vascular smooth muscle. Immunohistochemistry was adopted to confirm the existence and the distribution of β₃-AR in rat thoracic aorta.

RESULTSThe results showed that: (1) The thoracic aorta was relaxed by β₃-AR activation, with a relaxation percentage of (10.59 ± 0.79). (2) β₃-AR was expressed in both endothelial and smooth muscle layer in thoracic aorta sections of rats. (3) PRA did not block the effect of BRL on the thoracic aorta. The relaxation actions of BRL could be antagonized by pre-incubating the thoracic aorta with SR. (4) L-NNA (a NOS inhibitor) and H-89 (a PKA inhibitor) reversed the relaxation effect of BRL on vascular smooth muscle. (5) The effect of BRL was decreased after application of Ibriotoxin (IBTX), a large conductance calcium dependent potassium channel blocker.

CONCLUSIONThe results confirmed that activation of β₃-AR led to relaxation of thoracic aorta smooth muscle. The relaxation action of β₃-AR on smooth muscle of rat thoracic aorta was related to activation of NOS and PKA signaling pathway. Large conductance Ca²⁺-K⁺ channels were involved in the relaxation action of β₃-AR activation on rat thoracic aorta smooth muscle.

Animals ; Aorta, Thoracic ; physiology ; In Vitro Techniques ; Isoquinolines ; Large-Conductance Calcium-Activated Potassium Channels ; physiology ; Muscle Contraction ; Muscle Relaxation ; Muscle, Smooth, Vascular ; physiology ; Nitroarginine ; Peptides ; Propanolamines ; Propranolol ; Rats ; Receptors, Adrenergic, beta-3 ; physiology ; Signal Transduction ; Sulfonamides