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Aim: To identify the mechanisms of P2X3 receptor inhibition by extracellular cyclic adenosine monophosphate (cAMP) in rat dorsal root ganglion (DRG) neurones. Methods: Whole-cell currents were measured in cultured DRG neurones using the combination of voltage and concentration clamp. Results: We have found that extracellular cAMP inhibits P2X3-mediated currents in a concentration- and use-dependent manner. The P2X3 currents, activated by ATP applied every 4 min, were inhibited by 55% in the presence of 10 μm cAMP and by 81% in the presence of 30 μm cAMP. At 8 min interval between ATP applications the same concentration of cAMP did not alter the currents. Addition of 0.5 mm of guanosine 5′- O-(2-thiodiphosphate) to intracellular solution blocked the inhibitory action of cAMP. The inhibitory effects of cAMP were not mimicked by extracellular application of 30 μm adenosine. Conclusions: In this paper, we demonstrate, for the first time, that extracellular application of cAMP to rat sensory neurones inhibits P2X3 receptors via a G protein-coupled mechanism in a use-dependent manner, thus indicating the neuronal expression of specific plasmalemmal cAMP receptor. [ABSTRACT FROM AUTHOR]

Aim: Investigate whether juvenile exercise could induce a long‐term muscle memory, boosting the effects of exercise in adults. Methods: We devised a 5‐week climbing exercise scheme with food reward administered to male juvenile rats (post‐natal week 4–9). Subsequently, the animals were subjected to 10 weeks of detraining (week 9–19) without climbing and finally retraining during week 19–21. Results: The juvenile exercise increased fiber cross‐sectional area (fCSA) by 21% (p = 0.0035), boosted nuclear accretion by 13% (p = 0.057), and reduced intraperitoneal fat content by 28% (p = 0.007) and body weight by 9% (p = 0.001). During detraining, the fCSA became similar in the animals that had been climbing compared to naive controls, but the elevated number of myonuclei induced by the climbing were maintained (15%, p = 0.033). When the naive rats were subjected to 2 weeks of adult exercise there was little effect on fCSA, while the previously trained rats displayed an increase of 19% (p = 0.0007). Similarly, when the rats were subjected to unilateral surgical overload in lieu of the adult climbing exercise, the increase in fCSA was 20% (p = 0.0039) in the climbing group, while there was no significant increase in naive rats when comparing to the contralateral leg. Conclusion: This demonstrates that juvenile exercise can establish a muscle memory boosting the effects of adult exercise. The juvenile climbing exercise with food reward also led to leaner animals with lower body weight. These differences were to some extent maintained throughout the adult detraining period in spite of all animals being fed ad libitum, indicating a form of body weight memory. [ABSTRACT FROM AUTHOR]

Aim: To develop a method for direct measurement of the fluorescent d‐glucose analogue 2‐NBDG transport across the plasma membrane of single skeletal muscle fibres and derive the theoretical framework for determining the kinetic parameters for d‐glucose transport under basal conditions. Methods: A novel method is described for measuring free 2‐NBDG transport across plasma membrane of single rat muscle fibres at rest. The 2‐NBDG uptake was >90% suppressed by 100 µM cytochalasin B in both fast‐twitch and slow‐twitch fibres, indicating that the 2‐NBDG transport is GLUT‐mediated. Fibres were identified as fast‐twitch or slow‐twitch based on the differential sensitivity of their contractile apparatus to Sr2+. Results: The time course of 2‐NBDG uptake in the presence of 50 µM 2‐NBDG follows a one‐phase exponential plateau curve and is faster in fast‐twitch (rate constant 0.053 ± 0.0024 s‐1) than in slow‐twitch fibres (rate constant 0.031 ± 0.0021 s‐1). The rate constants were markedly reduced in the presence of 20 mM d‐glucose to 0.0082 ± 0.0004 s‐1 and 0.0056 ± 0.0002 s‐1 in fast‐twitch and slow‐twitch fibres respectively. 2‐NBDG transport was asymmetric, consistent with GLUT1 being the major functional GLUT isoform transporting 2‐NBDG in muscle fibres at rest. The parameters describing the transport kinetics for both 2‐NBDG and d‐glucose (dissociation constants, Michaelis–Menten constants, maximal rates of uptake and outflow) were calculated from the measurements made with 2‐NBDG. Conclusion: Free 2‐NBDG and d‐glucose transport across the plasma membrane of single rat muscle fibres at rest is fast, conclusively showing that the rate‐limiting step in d‐glucose uptake in skeletal muscle is not necessarily the GLUT‐mediated transport of d‐glucose. [ABSTRACT FROM AUTHOR]

Aim: Kidney diseases constitute a major health challenge, which requires noninvasive imaging to complement conventional approaches to diagnosis and monitoring. Several renal pathologies are associated with changes in kidney size, offering an opportunity for magnetic resonance imaging (MRI) biomarkers of disease. This work uses dynamic MRI and an automated bean‐shaped model (ABSM) for longitudinal quantification of pathophysiologically relevant changes in kidney size. Methods: A geometry‐based ABSM was developed for kidney size measurements in rats using parametric MRI (T2, T2* mapping). The ABSM approach was applied to longitudinal renal size quantification using occlusion of the (a) suprarenal aorta or (b) the renal vein, (c) increase in renal pelvis and intratubular pressure and (d) injection of an X‐ray contrast medium into the thoracic aorta to induce pathophysiologically relevant changes in kidney size. Results: The ABSM yielded renal size measurements with accuracy and precision equivalent to the manual segmentation, with >70‐fold time savings. The automated method could detect a ~7% reduction (aortic occlusion) and a ~5%, a ~2% and a ~6% increase in kidney size (venous occlusion, pelvis and intratubular pressure increase and injection of X‐ray contrast medium, respectively). These measurements were not affected by reduced image quality following administration of ferumoxytol. Conclusion: Dynamic MRI in conjunction with renal segmentation using an ABSM supports longitudinal quantification of changes in kidney size in pathophysiologically relevant experimental setups mimicking realistic clinical scenarios. This can potentially be instrumental for developing MRI‐based diagnostic tools for various kidney disorders and for gaining new insight into mechanisms of renal pathophysiology. [ABSTRACT FROM AUTHOR]

Aim: Our previous studies have demonstrated the importance of dietary factors in the determination of hypertension in Dahl salt‐sensitive (SS) rats. Since the gut microbiota has been implicated in chronic diseases like hypertension, we hypothesized that dietary alterations shift the microbiota to mediate the development of salt‐sensitive hypertension and renal disease. Methods: This study utilized SS rats from the Medical College of Wisconsin (SS/MCW) maintained on a purified, casein‐based diet (0.4% NaCl AIN‐76A, Dyets) and from Charles River Laboratories (SS/CRL) fed a whole grain diet (0.75% NaCl 5L79, LabDiet). Faecal 16S rDNA sequencing was used to phenotype the gut microbiota. Directly examining the contribution of the gut microbiota, SS/CRL rats were administered faecal microbiota transfer (FMT) experiments with either SS/MCW stool or vehicle (Vehl) in conjunction with the HS AIN‐76A diet. Results: SS/MCW rats exhibit renal damage and inflammation when fed high salt (HS, 4.0% NaCl AIN‐76A), which is significantly attenuated in SS/CRL. Gut microbiota phenotyping revealed distinct profiles that correlate with disease severity. SS/MCW FMT worsened the SS/CRL response to HS, evidenced by increased albuminuria (67.4 ± 6.9 vs 113.7 ± 25.0 mg/day, Vehl vs FMT, P =.007), systolic arterial pressure (158.6 ± 5.8 vs 177.8 ± 8.9 mmHg, Vehl vs FMT, P =.09) and renal T‐cell infiltration (1.9‐fold). Amplicon sequence variant (ASV)‐based analysis of faecal 16S rDNA sequencing data revealed taxa that significantly shifted with FMT: Erysipelotrichaceae_2, Parabacteroides gordonii, Streptococcus alactolyticus, Bacteroidales_1, Desulfovibrionaceae_2, Ruminococcus albus. Conclusions: These data demonstrate that dietary modulation of the gut microbiota directly contributes to the development of Dahl SS hypertension and renal injury. [ABSTRACT FROM AUTHOR]

Aim: It is debated whether the inhibition of glucagon secretion by glucose results from direct effects of glucose on the α‐cell (intrinsic regulation) or by paracrine effects exerted by beta‐ or delta‐cell products. Methods: To study this in a more physiological model than isolated islets, we perfused isolated rat pancreases and measured glucagon, insulin and somatostatin secretion in response to graded increases in perfusate glucose concentration (from 3.5 to 4, 5, 6, 7, 8, 10, 12 mmol/L) as well as glucagon responses to blockage/activation of insulin/GABA/somatostatin signalling with or without addition of glucose. Results: Glucagon secretion was reduced by about 50% (compared to baseline secretion at 3.5 mmol/L) within minutes after increasing glucose from 4 to 5 mmol/L (P <.01, n = 13). Insulin secretion was increased minimally, but significantly, compared to baseline (3.5 mmol/L) at 4 mmol/L, whereas somatostatin secretion was not significantly increased from baseline until 7 mmol/L. Hereafter secretion of both increased gradually up to 12 mmol/L glucose. Neither recombinant insulin (1 µmol/L), GABA (300 µmol/L) or the insulin‐receptor antagonist S961 (at 1 µmol/L) affected basal (3.5 mmol/L) or glucose‐induced (5.0 mmol/L) attenuation of glucagon secretion (n = 7‐8). Somatostatin‐14 attenuated glucagon secretion by ~ 95%, and blockage of somatostatin‐receptor (SSTR)‐2 or combined blockage of SSTR‐2, −3 and −5 by specific antagonists increased glucagon output (at 3.5 mmol/L glucose) and prevented glucose‐induced (from 3.5 to 5.0 mmol/L) suppression of secretion. Conclusion: Somatostatin is a powerful and tonic inhibitor of glucagon secretion from the rat pancreas and is required for glucose to inhibit glucagon secretion. [ABSTRACT FROM AUTHOR]

The author talks about a study published in the issue focusing on the gene expression and delayed nephrogenesis in growth-restricted foetus and neonate of a rat. Topics discussed include the abundance of branching morphogenesis genes in the neonate, the focus on the role of leptin signalling, and the approximation of uteroplacental insufficiency through uterine vessel ligation.

Aim To examine whether sympathetic afferent stimulation ( SAS) inhibits central vagal activation induced by α2-adrenergic stimulation. Methods In anaesthetized Wistar-Kyoto rats, a cardiac microdialysis technique was applied to the left ventricle, and the effect of α2-adrenergic stimulation by medetomidine on myocardial interstitial acetylcholine ( ACh) levels was examined in the absence ( n = 6) or the presence ( n = 6) of SAS delivered from the left stellate ganglion. The effect of electrical vagal efferent stimulation on myocardial interstitial ACh release was also examined in the absence or the presence of SAS ( n = 6). Results Intravenous medetomidine (0.1 mg kg−1) significantly increased myocardial interstitial ACh levels in the absence of SAS (from 1.95 ± 0.79 to 3.36 ± 1.61 n m, P < 0.05), but not in the presence of SAS (from 1.67 ± 0.67 to 2.01 ± 0.78 n m). In contrast, electrical vagal nerve stimulation increased myocardial interstitial ACh level to the same degree regardless of SAS (from 1.66 ± 0.16 to 3.93 ± 0.72 n m without SAS vs. 4.05 ± 0.89 n m with SAS). Conclusion Sympathetic afferent stimulation inhibited medetomidine-induced ACh release, but not electrical stimulation-induced ACh release, suggesting that SAS inhibited medetomidine-induced vagal activation via central mechanisms. While central vagal activation by α2-adrenergic agonists could be an alternative to electrical vagal activation, blocking sympathetic afferent input may be important to increase the efficacy of α2-adrenergic agonists in enhancing vagal nerve activity. [ABSTRACT FROM AUTHOR]

The functions of the lower urinary tract to store and periodically eliminate urine are regulated by a complex neural control system in the brain and spinal cord that coordinates the activity of the bladder and urethral outlet. Experimental studies in animals indicate that urine storage is modulated by reflex mechanisms in the spinal cord, whereas voiding is mediated by a spinobulbospinal pathway passing through a coordination centre in the rostral brain stem. Many of the neural circuits controlling micturition exhibit switch-like patterns of activity that turn on and off in an all-or-none manner. This study summarizes the anatomy and physiology of the spinal and supraspinal micturition switching circuitry and describes a computer model of these circuits that mimics the switching functions of the bladder and urethra at the onset of micturition. [ABSTRACT FROM AUTHOR]

Aim Extracellular nucleotides activate cell-surface purinergic ( P2) receptors, contribute to the local regulation of vascular tone and play important roles in pathophysiological states. However, little is known about the vasodilator effects of P2 Y1-receptor activation in diabetic states. We hypothesized that in a model of established type 1 diabetes, long-term streptozotocin ( STZ)-induced diabetic rats, the arterial relaxation elicited by a P2 Y1-receptor agonist would be impaired. Methods Relaxations to adenosine 5′-diphosphate sodium salt ( ADP), 2- Me SADP (selective P2 Y1-receptor agonist) and adenosine 5′-triphosphate disodium salt ( ATP) were examined in superior mesenteric artery rings from long-term STZ-induced diabetic rats (at 50-57 weeks after STZ injection). ADP-stimulated nitric oxide ( NO) production in the superior mesenteric artery was assessed by measuring the levels of NO metabolites. Mesenteric artery expressions of P2 Y1 receptor, and ADP-stimulated levels of phosphorylated endothelial NO synthase (e NOS) (at Ser1177 and at Thr495) and e NOS were detected by Western blotting. Results Arteries from diabetic rats exhibited (vs. those from age-matched control rats): (i) reduced ADP-induced relaxation, which was partly or completely inhibited by endothelial denudation, by NOS inhibitor treatment and by a selective P2 Y1-receptor antagonist, (ii) reduced 2- Me SADP-induced relaxation, (iii) reduced ADP-stimulated release of NO metabolites and (iv) impaired ADP-induced stimulation of e NOS activity (as evidenced by reduced the fold increase in e NOS phosphorylation at Ser1177 with no difference in fold increase in e NOS phosphorylation at Thr495). The protein expression of P2 Y1 receptor did not differ between diabetic and control arteries. Conclusions These results suggest that P2 Y1-receptor-mediated vasodilatation is impaired in superior mesenteric arteries from long-term type 1 diabetic rats. This impairment is because of reduced P2 Y1-receptor-mediated NO signalling, rather than to reduced P2 Y1-receptor expression. [ABSTRACT FROM AUTHOR]

Aim To elucidate the abnormality of vagal control in spontaneously hypertensive rats ( SHR) by measuring left ventricular myocardial interstitial acetylcholine ( ACh) release in response to α2-adrenergic stimulation as an index of in vivo vagal nerve activity. Methods A cardiac microdialysis technique was applied to the rat left ventricle in vivo, and the effect of α2-adrenergic stimulation by medetomidine or electrical vagal nerve stimulation on myocardial interstitial ACh levels was examined in normotensive Wistar-Kyoto rats ( WKY) and SHR under anaesthetized conditions. Results Intravenous medetomidine (0.1 mg kg−1) significantly increased the ACh levels in WKY (from 2.4 ± 0.6 to 4.2 ± 1.3 nmol L−1, P < 0.05, n = 7) but not in SHR (from 2.5 ± 0.7 to 2.7 ± 0.7 nmol L−1, n = 7). In contrast, electrical vagal nerve stimulation increased the ACh levels in both WKY (from 1.0 ± 0.4 to 2.9 ± 0.9 nmol L−1, P < 0.001, n = 6) and SHR (from 0.9 ± 0.2 to 2.2 ± 0.4 nmol L−1, P < 0.001, n = 6). Intravenous administration of medetomidine (0.1 mg kg−1) did not affect the vagal nerve stimulation-induced ACh release in either WKY or SHR. Conclusion Medetomidine-induced central vagal activation was impaired in SHR, whereas peripheral vagal control of ACh release was preserved. In addition to abnormal sympathetic control, vagal control by the central nervous system may be impaired in SHR. [ABSTRACT FROM AUTHOR]

Aim: The purpose was to evaluate the effects of fatiguing eccentric contractions (EC) on calcium (Ca2+) handling properties in mammalian type I muscles. We hypothesized that EC reduces both endogenous sarcoplasmic reticulum (SR) content of releasable Ca2+ (eSRCa2+) and myofibrillar Ca2+ sensitivity. Methods: Isolated rat soleus muscles performed 30 EC bouts. Single fibres were isolated from the muscle and after mechanical removal of sarcolemma used to measure eSRCa2+, rate of SR Ca2+ loading and myofibrillar Ca2+ sensitivity. Results: Following EC maximal force in whole muscle was reduced by 30% and 16/100 Hz force ratio by 33%. The eSRCa2+ in fibres from non-stimulated muscles was 45 ± 5% of the maximal loading capacity. After EC, eSRCa2+ per fibre CSA decreased by 38% ( P = 0.05), and the maximal capacity of SR Ca2+ loading was depressed by 32%. There were no effects of EC on either myofibrillar Ca2+ sensitivity, maximal Ca2+ activated force per cross-sectional area and rate of SR Ca2+ loading, or in SR vesicle Ca2+ uptake and release. Conclusions: We conclude that EC reduces endogenous SR content of releasable Ca2+ but that myofibrillar Ca2+ sensitivity and SR vesicle Ca2+ kinetics remain unchanged. The present data suggest that the long-lasting fatigue induced by EC, which was more pronounced at low frequencies (low frequency fatigue), is caused by reduced Ca2+ release occurring secondary to reduced SR content of releasable Ca2+. [ABSTRACT FROM AUTHOR]

Aim: To assess the effect of the oestral cycle on the respiratory mechanics of the rat. Methods: We measured the main mechanical respiratory parameters, namely respiratory system and lung resistances and compliances, by the end-inflation occlusion method on two populations of female rats, during proestrous–oestrous and metaoestrous–diestrous phases. Results: Inflation–deflation loops of the lungs were found to be statistically higher in rats during metaoestrous–diestrous phase. No other statistically significant difference was found in the measured mechanical respiratory parameters. Conclusion: Our results suggest that the naturally occurring fluctuations in serum sexual hormone levels during the sexual cycle influence the lung's hysteresis but do not influence the respiratory system and lung resistances or static compliances. A possible effect of female sexual hormones on surfactant activity is also suggested. [ABSTRACT FROM AUTHOR]

Aim: To determine the influence of inflammation on salivary secretion. Secretion by salivary glands involves interactions between nerves, blood vessels and salivary cells. The present study investigated the effects of inflammation on rat submandibular gland function following acute ductal obstruction. Methods: Under recovery anaesthesia a metal clip was placed on the main duct of the submandibular gland. After 24 h salivary secretion was evoked by nerve and methacholine stimulation. For recovery experiments the clip was removed after 24 h and the animal left to recover for 3 days when salivary function was again assessed. Results: By 24 h of obstruction an inflammatory infiltrate had developed within the obstructed gland and stimulated salivary flows were just 20% of the normal secretion, whilst protein secretion and ion reabsorption were also severely impaired. If ductal obstruction was removed after 24 h the salivary function returned to normal after 3 days of recovery. In vitro analysis of cells from 24-h ligated glands revealed normal changes in intracellular calcium (the main secondary messenger involved in fluid secretion) in response to methacholine stimulation. Protein secretion from isolated cells indicated some changes in particular to methacholine-induced protein secretion although a significant protein secretion was still seen in response to isoprenaline – the main stimulus for protein secretion. Conclusion: This report demonstrates reversible salivary inhibition associated with an inflammatory infiltrate within the salivary gland. [ABSTRACT FROM AUTHOR]

Aim: The incidence of hydronephrosis due to ureteropelvic junction obstruction is approx. 0.5%. During the last decade, the management of non-symptomatic hydronephrosis has become much more conservative, but the long-term physiological consequences of this policy are not clear. Previously, we have shown that animals with chronic partial unilateral ureteral obstruction develop salt-sensitive hypertension. In this study, the effects of ipsilateral and contralateral nephrectomy and ureterovesicostomy on blood pressure were studied in hydronephrotic animals. Methods: Partial unilateral ureteral obstruction was created in 3-week-old male Sprague–Dawley rats and blood pressure was measured telemetrically 4–6 weeks later during a normal and high salt diet before and after uninephrectomy or ureterovesicostomy. Plasma samples for renin assay were collected during both diets before and after ipsilateral nephrectomy. Results: All hydronephrotic animals developed salt-sensitive hypertension, of different degrees. Before nephrectomy the plasma renin concentration was significantly higher in the hydronephrotic animals than in controls (160 ± 15 μGU mL−1 vs. 96 ± 12 μGU mL−1, respectively), but after the ipsilateral nephrectomy no differences were found between the groups. In the hydronephrotic animals both ipsilateral nephrectomy and ureterovesicostomy reduced the blood pressure and salt-sensitivity but the former still differed significantly from the controls. In contralaterally, nephrectomized hydronephrotic animals the salt-sensitive hypertension became more pronounced. Conclusion: Hydronephrosis in rats causes salt-sensitive hypertension that can be markedly reduced by removing the hydronephrotic kidney or relieving the obstruction by ureterovesicostomy. The mechanisms appear to be intrarenal and primarily located in the diseased kidney, but a secondary mechanism is also present. [ABSTRACT FROM AUTHOR]

Aim: The renal tubular uptake of 125I-Aprotinin (*Ap) is on average located more superficially than its filtration site, causing transfer of some of *Ap filtered in deep to more superficial cortical zones. 125I-Cystatin C (*Cy) showed less uptake in deep cortical zones than Ap, suggesting a longer and/or a more superficial tubular uptake site. To test that hypothesis and to quantify the outward transfer of the filtered polypeptides, we estimated the tubular uptake pattern of the tracers in perfusion fixed rat kidneys after intravenous injection of *Cy and *Ap. Methods: Autoradiographs were made from 10 μm thick slices of Microfil nephron casts from outer (OC), middle (MC) and inner (IC) cortical zones to quantify cortical border-crossing *Ap transfer. Single nephron glomerular filtration rate (snGFR) was estimated as the zonal uptake of *Ap corrected for *Ap transfer, divided by its time-integrated plasma concentration and the zonal number of glomeruli. Results: *Ap and *Cy uptake fell exponentially along the proximal convoluted tubule (PCT), indicating an uptake proportional to luminal concentration. Uptake in IC exceededx that in MC and OC nephrons. The per cent PCT length with *Cy uptake (67.2 ± 1.6) exceeded that of *Ap (54.6 ± 1.8). The zonal border-crossing PCT length (29–34% of total PCT) from deep to more superficial cortical zones transferred 4–6% more *Cy than *Ap. Conclusion: Greater tubular uptake length of *Cy than of *Ap causes more cortical border-crossing of *Cy. The zonal snGFR estimated from Aprotinin uptake corrected for border-crossing agreed well with that obtained with the Hanssen ferrocyanide technique. [ABSTRACT FROM AUTHOR]

Aim: Effects of submaximal stimulation frequencies on myofascial force transmission were investigated for rat anterior crural muscles with all motor units activated. Methods: Tibialis anterior and extensor hallucis longus (TAEHL) muscles were kept at constant muscle–tendon complex length, but extensor digitorum longus muscle (EDL) was lengthened distally. All muscles were activated simultaneously at 10, 20, 30 and 100 Hz within an intact anterior crural compartment. Results: At lower frequencies, significant proximo-distal EDL force differences exist. Absolute EDL proximo-distal active force differences were highest at 100 Hz (Δ Fdist-prox = 0.4 N). However, the normalized difference was highest at 10 Hz (Δ Fdist-prox = 30% Fdist). Firing-frequency dependent shifts of the ascending limb of the EDL length–force curve to higher lengths were confirmed for a muscle within an intact compartment, although effects of firing frequency assessed at proximal and distal EDL tendons differed quantitatively. As EDL was lengthened distally, TAEHL distal isometric active force decreased progressively. The absolute decrease was highest for 100 Hz (Δ Ffrom initial = −0.25 N). However, the highest normalized decrease was found for 10 Hz stimulation (Δ Ffrom initial = −40%). Conclusions: At submaximal stimulation frequencies, myofascial force transmission is present and the fraction of force transmitted myofascially increases with progressively lower firing frequencies. Evidently, the stiffness of epimuscular myofascial paths of force transmission decreases less than the stiffness of serial sarcomeres and myotendinous pathways. It is concluded that low firing frequencies as encountered in vivo enhance the relative importance of epimuscular myofascial force transmission with respect to myotendinous force transmission. [ABSTRACT FROM AUTHOR]

Aim: mTORC1 is regarded as an important key regulator of protein synthesis and hypertrophy following mechanical stimuli in skeletal muscle. However, as excitation and tension development is tightly coupled in most experimental models, very little and largely indirect evidence exist for such a mechanosensitive pathway. Here, we sought to examine whether activation of mTORC1 signalling is dependent on tension per se in rat skeletal muscle. Methods: To examine the mechanosensitivity of mTORC1, rat EDL muscles were exposed to either excitation‐induced eccentric contractions (ECC), passive stretching (PAS) with identical peak tension (Tpeak) and Tension‐Time‐Integral (TTI), or ECC with addition of inhibitors of the myosin ATPases (IMA). To further explore the relationship between tension and mTORC1 signalling, rat EDL muscles were subjected to PAS of different magnitudes of Tpeak while standardizing TTI and vice versa. Results: PAS and ECC with equal Tpeak and TTI produced similar responses in mTORC1 signalling despite different modes of tension development. When active tension during ECC was nearly abolished by addition of IMA, mTORC1 signalling was reduced to a level comparable to non‐stimulated controls. In addition, when muscles were exposed to PAS of varying levels of Tpeak with standardized TTI, activation of mTORC1 signalling displayed a positive relationship with peak tension. Conclusions: The current study directly links tension per se to activation of mTORC1 signalling, which is independent of an active EC‐coupling sequence. Moreover, activation of mTORC1 signalling displays a positive dose‐response relationship with peak tension. [ABSTRACT FROM AUTHOR]