scholarly journals Constraints on the deformation of the vibrissa within the follicle

2020 ◽  
Author(s):  
Yifu F. Luo ◽  
Chris S. Bresee ◽  
John W. Rudnicki ◽  
Mitra J. Z. Hartmann
Keyword(s):  
Blood Pressure ◽  
Muscle Contraction ◽  
Mechanical Model ◽  
Ex Vivo ◽  
Surrounding Tissue ◽  
Tactile Sensation ◽  
Tactile Sensitivity ◽  
Neural Signals ◽  
Intrinsic Muscle ◽  
Using Data

AbstractNearly all mammals have a vibrissal system specialized for tactile sensation, composed of whiskers growing from sensor-rich follicles in the skin. Because a whisker has no sensors along its length, an open question is how mechanoreceptors in the follicle transduce sensory signals. These mechanoreceptors are activated by whisker deflection, so it is essential to understand how the whisker deforms within the follicle and so how it may activate different populations of mechanoreceptors in different ways. During active whisking behaviors, muscle contractions and increases in blood pressure in the ring sinus will likely affect the whisker deformation profile. Directly recording from mechanoreceptors under these conditions is difficult due to their small size, location within intricate and delicate membranes, and movement during sensation. Using data from a previous experimental study on whisker deflection, and from histological analysis of follicle tissue, we develop a mechanical model of the follicle sinus complex. With this model we first simulate passive whisker contact, replicating previous results of ex vivo experiments on deformation of a whisker within the follicle. We then simulate whisker deformation within the follicle during active whisking. Results of these simulations predict that both intrinsic muscle contraction and elevated hydrostatic pressure within the ring sinus may be regulatory mechanisms to enhance tactile sensitivity during active whisking. The mechanical model presented in this study is an important first step in simulating mechanical interactions within whisker follicles, and aids in the development of artificial robotic follicles.Author summaryMany mammals rely on whiskers as a mode of tactile sensation, especially when exploring in darkness. Active, rhythmic protraction and retraction of the whiskers, commonly referred to as whisking, is observed among many whisker specialist animals. Whisker-based sensing requires the forces and moments generated by external stimuli to be transduced into neural signals inside the follicle, which holds the base of the whisker shaft. Within the follicle, the interaction between the whisker’s deformation and the surrounding tissue determines how different groups of mechanoreceptors along the inside of a follicle will deformed. However, experimental measurement of this interaction is challenging to perform in active animals. We therefore created a mechanical model for the follicle sinus complex to simulate whisker deformation within the follicle resulting from external whisker deflection. Our simulations replicate results from previous ex vivo experiments that have monitored whisker deformation in the follicle ring sinus. We extend these results by predicting whisker deformation profiles during active whisking. Our results suggest that both intrinsic muscle contraction and an increase in blood pressure will affect the whisker deformation profile within the follicle, and in turn, the tactile sensitivity of the whisker system.

scholarly journals Constraints on the deformation of the vibrissa within the follicle

2021 ◽  
Vol 17 (4) ◽  
pp. e1007887
Author(s):  
Yifu Luo ◽  
Chris S. Bresee ◽  
John W. Rudnicki ◽  
Mitra J. Z. Hartmann
Keyword(s):  
Blood Pressure ◽  
Mechanical Model ◽  
Histological Analysis ◽  
Ex Vivo ◽  
Primary Afferents ◽  
Muscle Stiffness ◽  
Tactile Sensation ◽  
Tactile Sensitivity ◽  
Passive Touch ◽  
Novel Model

Nearly all mammals have a vibrissal system specialized for tactile sensation, composed of whiskers growing from sensor-rich follicles in the skin. When a whisker deflects against an object, it deforms within the follicle and exerts forces on the mechanoreceptors inside. In addition, during active whisking behavior, muscle contractions around the follicle and increases in blood pressure in the ring sinus will affect the whisker deformation profile. To date, however, it is not yet possible to experimentally measure how the whisker deforms in an intact follicle or its effects on different groups of mechanoreceptors. The present study develops a novel model to predict vibrissal deformation within the follicle sinus complex. The model is based on experimental results from a previous ex vivo study on whisker deformation within the follicle, and on a new histological analysis of follicle tissue. It is then used to simulate whisker deformation within the follicle during passive touch and active whisking. Results suggest that the most likely whisker deformation profile is “S-shaped,” crossing the midline of the follicle right below the ring sinus. Simulations of active whisking indicate that an increase in overall muscle stiffness, an increase in the ratio between deep and superficial intrinsic muscle stiffness, and an increase in sinus blood pressure will all enhance tactile sensitivity. Finally, we discuss how the deformation profiles might map to the responses of primary afferents of each mechanoreceptor type. The mechanical model presented in this study is an important first step in simulating mechanical interactions within whisker follicles.

scholarly journals Reduced biomechanical models for precision-cut lung-slice stretching experiments

2021 ◽  
Vol 82 (5) ◽  
Author(s):  
Hannah J. Pybus ◽  
Amanda L. Tatler ◽  
Lowell T. Edgar ◽  
Reuben D. O’Dea ◽  
Bindi S. Brook
Keyword(s):  
Smooth Muscle ◽  
Muscle Contraction ◽  
Ex Vivo ◽  
Finite Thickness ◽  
Biomechanical Model ◽  
Local Stress ◽  
Smooth Muscle Contraction ◽  
Biomechanical Models ◽  
Cytokine Activation ◽  
Asymptotic Reduction

AbstractPrecision-cut lung-slices (PCLS), in which viable airways embedded within lung parenchyma are stretched or induced to contract, are a widely used ex vivo assay to investigate bronchoconstriction and, more recently, mechanical activation of pro-remodelling cytokines in asthmatic airways. We develop a nonlinear fibre-reinforced biomechanical model accounting for smooth muscle contraction and extracellular matrix strain-stiffening. Through numerical simulation, we describe the stresses and contractile responses of an airway within a PCLS of finite thickness, exposing the importance of smooth muscle contraction on the local stress state within the airway. We then consider two simplifying limits of the model (a membrane representation and an asymptotic reduction in the thin-PCLS-limit), that permit analytical progress. Comparison against numerical solution of the full problem shows that the asymptotic reduction successfully captures the key elements of the full model behaviour. The more tractable reduced model that we develop is suitable to be employed in investigations to elucidate the time-dependent feedback mechanisms linking airway mechanics and cytokine activation in asthma.

Abstract P466: Circadian Rhythm Disruptions in a Novel Diabetic db/db-mPer2 Luc Mouse Model

Hypertension ◽  
2017 ◽  
Vol 70 (suppl_1) ◽  
Author(s):  
Tianfei Hou ◽  
Wen Su ◽  
Ming C Gong ◽  
Zhenheng Guo
Keyword(s):  
Blood Pressure ◽  
Circadian Rhythms ◽  
Real Time ◽  
Clock Gene ◽  
Ex Vivo ◽  
Phase Advance ◽  
Luciferase Reporter ◽  
High Time Resolution ◽  
Peripheral Tissues

Db/db mouse, which lacks functional leptin receptor, is an extensively used model of obesity and type 2 diabetes. We and others have demonstrated that db/db mouse has disruptions in circadian rhythms of behavior, physiology and some clock genes. However, systemic investigations of the alterations in clock gene oscillations in multiple systems with high time resolution in this model are impeded by the impractical demand for large number of animals. To overcome this limitation, we cross bred the db/db mouse with mPer2 Luc mouse in which the clock gene Period2 is fused with a luciferase reporter thus allow real-time monitoring of the clock gene Per2 oscillations. The generated db/db-mPer2 Luc mice had the typical diabetic mellitus including obesity, hyperglycemia, hyperinsulinemia, glucose intolerance and insulin resistance. In addition, the db/db-mPer2 Luc mice also exhibited disruptions in circadian rhythms in behavior (locomotor activity), physiology (blood pressure) and metabolism (respiratory exchange ratio and energy expenditure). Using the LumiCycle system, we monitored in real-time of the Per2 oscillations in both the SCN central clock and multiple peripheral tissues ex vivo . The results showed no difference in the phase of the central SCN Per2 oscillation. However, the peripheral tissues that related to metabolism, such as liver and white adipose clocks, displayed 3.28±0.86 and 4.64±1.06 hours of phase advance respectively. Aorta, mesentery artery and kidney, organs play important role in blood pressure homeostasis, showed 0.99±0.37, and 2.12±0.4, and 2.21±0.5 hours phase advance respectively. Interestingly, no difference was observed in the lung and adrenal gland. We then investigated the Per2 oscillation in vivo by using the IVIS imaging system. Consistent with the ex vivo results, the liver Per2 oscillation were phase advanced in vivo. Our findings demonstrated that clock gene Per2 oscillations were disrupted in multiple peripheral tissues but not in central SCN. Moreover, the extent of phase advance in peripheral tissue varies largely. Our results suggest dyssynchrony of the clock oscillations among various peripheral systems likely contribute to the multiple disruptions in physiology and metabolism in diabetic db/db mice.

An ionic-chemical-mechanical model for muscle contraction

Biopolymers ◽  
2016 ◽  
Vol 105 (12) ◽  
pp. 887-897 ◽  
Author(s):  
Gerald S. Manning
Keyword(s):  
Muscle Contraction ◽  
Mechanical Model

Indole-3-propionic acid, a tryptophan-derived bacterial metabolite, increases blood pressure via cardiac and vascular mechanisms in rats

2021 ◽  
Author(s):  
Piotr Konopelski ◽  
Dawid Chabowski ◽  
Marta Aleksandrowicz ◽  
Ewa Kozniewska ◽  
Piotr Podsadni ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Propionic Acid ◽  
Metabolic Activity ◽  
Ex Vivo ◽  
Circulatory System ◽  
Cardiovascular Responses ◽  
Gut Bacteria ◽  
Qtc Interval ◽  
Resistance Arteries ◽  
Wistar Kyoto

Objectives. Recent evidence suggests that gut bacteria-derived metabolites interact with the cardiovascular system and alter blood pressure (BP) in mammals. Here, we evaluated the effect of indole-3-propionic acid (IPA), a gut bacteria-derived metabolite of tryptophan, on the circulatory system. Methods. Arterial BP, electrocardiographic and echocardiographic (ECHO) parameters were recorded in male, anesthetized, 12-week-old Wistar-Kyoto rats at baseline and after intravenous administration of either IPA or vehicle. In additional experiments, rats were pretreated with prazosin or pentolinium to evaluate the involvement of the autonomic nervous system in cardiovascular responses to IPA. IPA's concentrations were measured using UHPLC-MS. The reactivity of endothelium-intact and -denuded mesenteric resistance arteries was tested. Cells' viability and LDH cytotoxicity assays were performed on cultured cardiomyocytes. Results. IPA increased BP with a concomitant bradycardic response but no significant change in QTc interval. The pretreatment with prazosin and pentolinium reduced the hypertensive response. ECHO showed increased contractility of the heart after the administration of IPA. Ex vivo, IPA constricted pre-dilated and endothelium-denuded mesenteric resistance arteries and increased metabolic activity of cardiomyocytes. Conclusions. IPA increases BP via cardiac and vascular mechanisms in rats. Furthermore, IPA increases cardiac contractility and metabolic activity of cardiomyocytes. Our study suggests that IPA may act as a mediator between gut microbiota and the circulatory system.

Abstract P183: Minimal Impact of JAMA 2014 Guidelines on Blood Pressure Control in a Large Health System

Circulation ◽  
2017 ◽  
Vol 135 (suppl_1) ◽  
Author(s):  
Alex R Chang ◽  
J E Hartle ◽  
Lawrence Appel ◽  
Morgan Grams
Keyword(s):  
Blood Pressure ◽  
Health System ◽  
Blood Pressure Control ◽  
Pressure Control ◽  
Mixed Effects Models ◽  
System Level ◽  
Minimal Impact ◽  
Before And After ◽  
Patients With Diabetes ◽  
Using Data

Background: JAMA 2014 blood pressure (BP) guidelines raised BP goals for adults older than 60 years (from <140/90 to <150/90) and adults with chronic kidney disease (CKD) or diabetes (from < 130/80 to <140/90). It is unknown whether there were changes in BP control at the health system level after guideline publication. Methods: Using data from 288,962 adults receiving primary care in the Geisinger Health System, we compared blood pressure control over 1-year time periods before and after the February 2014 publication of the JAMA 2014 BP guidelines (i.e. Aug 2012-July 2013 vs Aug 2014-July 2015). Mixed effects models were used, allowing intercepts to vary by individual, adjusted for age, gender, and race. Results: Mean age was 49.2 ± 18.3 y, 56.7% were female, and 2.5% were black. Prevalence of diagnoses for hypertension, diabetes, and CKD were 40.0%, 15.1%, and 11.4%, respectively. Overall, distributions of systolic BP were similar before and after JAMA 2014 BP guidelines (Figure). BP control <140/90 was also similar between the two periods for adults 18-59 y (90.9% vs. 90.3%; OR 1.01, 95% CI: 0.99-1.02; p=0.3), adults ≥ 60 y (81.8% vs 82.2%; OR 1.01, 95% CI: 1.00-1.03; p=0.05), and adults with diabetes (83.2% vs. 82.7%; OR 1.00, 95% CI: 0.99-1.02; p=0.7) whereas BP control <140/90 improved slightly for adults with CKD (81.7% vs. 82.1%; OR 1.06, 95% CI: 1.04-1.08; p<0.001). BP control <130/80 was marginally worse after JAMA 2014 BP guidelines in patients with diabetes (53.5% vs. 51.8%; OR 0.98, 95% CI: 0.96-0.99; p=0.01). Trends were similar in analyses only including patients with hypertension diagnoses (overall 78.6% vs. 78.2%, OR 1.00, 95% CI: 0.99-1.02; p=0.5), and when using a goal of < 130/80 for patients with CKD (53.3% vs. 53.5%; OR 1.06, 95% CI: 1.04-1.08; p<0.001). Conclusion: There was little change in blood pressure control in a large integrated health system after publication of the JAMA 2014 BP guidelines. These findings are reassuring given recent findings from the SPRINT trial supporting lower BP goals.

MO094SALT INFLUENCES UROMODULIN EXCRETION INDEPENDENT OF BLOOD PRESSURE

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Sheon Mary ◽  
Philipp Boder ◽  
Giacomo Rossitto ◽  
Lesley Graham ◽  
Kayley Scott ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Endoplasmic Reticulum ◽  
Direct Effect ◽  
Ex Vivo ◽  
Mrna Levels ◽  
Salt Loading ◽  
Spontaneously Hypertensive ◽  
Risk Variants ◽  
Wistar Kyoto

Abstract Background and Aims Uromodulin (UMOD) is the most abundant renal protein secreted into urine by the thick ascending epithelial (TAL) cells of the loop of Henle. Genetic studies have demonstrated an association between UMOD risk variants and hypertension. Studies on UMOD overexpressing transgenic mice have shown that UMOD increases the tubular salt reabsorption via enhanced NKCC2 activity. We aimed to dissect the effect of salt-loading and blood pressure on the excretion of UMOD. Method Wistar-Kyoto (WKY) and stroke-prone spontaneously hypertensive (SHRSP) rats (n=8/sex/strain) were maintained on 1% NaCl for three weeks. Salt-loaded SHRSP were treated with nifedipine. Tubule isolation and ex vivo incubation with nifedipine were used to assess its direct effect on TAL. Results Urinary UMOD excretion was significantly reduced after salt loading in both strains (figure). In salt-loaded SHRSP, nifedipine treatment reduced blood pressure and urinary UMOD excretion. The reductions in urinary UMOD excretion were dissociated from unchanged kidney UMOD protein and mRNA levels, however, were associated with UMOD endoplasmic reticulum accumulation, thus suggesting secretion as a key regulatory step. Ex vivo experiments with TAL tubules showed that nifedipine did not have a direct effect on UMOD secretion. Conclusion Our data suggest a direct effect of salt on UMOD secretion independent of blood pressure and a potential role of endoplasmic reticulum stress on the control of UMOD secretion. The role of UMOD as a cardiovascular risk marker deserves mechanistic reappraisal and further investigations based on our findings.

Abstract 19478: Endothelial and Cardiomyocyte -derived C-type Natriuretic Peptide Coordinate Heart Structure and Function

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Amie J Moyes ◽  
Sandy M Chu ◽  
Reshma S Baliga ◽  
Adrian J Hobbs
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Cardiac Function ◽  
Infarct Size ◽  
Natriuretic Peptide ◽  
Vascular Tone ◽  
Ex Vivo ◽  
Pressure Overload ◽  
Structure And Function ◽  
And Function

Background: Endothelium-derived C-type natriuretic peptide (CNP) plays a key vascular homeostatic role governing vascular tone, blood pressure, leukocyte flux, platelet reactivity and the integrity of the vessel wall. However, relatively little is known about physiological role(s) for endogenous CNP in regulating cardiac structure and function. Herein, we have utilised novel mouse strains with endothelium or cardiomyocyte -specific deletion of CNP to determine if the peptide modulates heart function under basal conditions and during cardiac stress. Methods: Blood pressure and ECG were assessed by radiotelemetry. A Langendorff heart model was used to study coronary vascular reactivity and ischemia-reperfusion (I/R) injury ex vivo. Echocardiography was performed to determine cardiac function at baseline and following pressure overload (trans-aortic constriction; 6 weeks) -induced left ventricular hypertrophy/heart failure. Results: Hearts from endothelium-specific CNP knockout (ecCNP KO) mice exhibited smaller reductions in coronary perfusion pressure (CPP) compared to wildtype (WT) littermates in response to the vasodilators bradykinin (ΔCPP: WT=31.7±2.7%, KO=21.1±2.9%, n=8, p<0.05) and acetylcholine (ΔCPP: WT=36.4±4.4%, KO=18.5±3.8%, n=6, p<0.05). Shear-stress induced coronary dilatation (i.e. reactive hyperaemia) was also blunted in ecCNP KO hearts (AUC: WT=2804±280 [a.u.], KO=1493±280 [a.u.], n=8, p<0.05). Under basal conditions the heart rate (BPM: WT=605±5, KO 579±4, n=5, p<0.001) and contractility (QA interval; WT=13.7±0.1ms, KO=14.8±0.1ms, n=5, p<0.001) were significantly reduced in cardiomyocyte-specific CNP (cmCNP) KO mice compared to WT. Myocardial infarct size was larger in cmCNP KO following I/R injury ex vivo (Infarct size: WT=14.1±6.3%, KO=21.8±1.8 %, n=6, p<0.05). Furthermore, cmCNP KO mice exhibited greater cardiac dysfunction following pressure-overload (e.g. fractional shortening: WT=34.4±0.9%, KO=30.5±1.4%, n=8, p<0.05). Conclusion: These data suggest that CNP of endothelial and cardiomyocyte origin preserves cardiac function and morphology via the regulation of coronary vascular tone, heart rate, and myocardial contractility/hypertrophy.

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