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 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.

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.

scholarly journals Molecular Mechanisms of Aroma Persistence: From Noncovalent Interactions Between Aroma Compounds and Oral Mucosa to Metabolization of Aroma Compounds by Saliva and Oral Cells

2021 ◽  
Author(s):  
Carolina Muñoz-Gonzalez ◽  
Marine Brulé ◽  
Christophe Martin ◽  
Gilles Feron ◽  
Francis Canon
Keyword(s):  
Oral Mucosa ◽  
Molecular Mechanisms ◽  
Ex Vivo ◽  
Noncovalent Interactions ◽  
Aroma Compounds ◽  
Integral Approach ◽  
Exhaled Air ◽  
Oral Cells ◽  
Novel Model

<p>Aroma persistence plays a major role in the liking and wanting of orally consumed products (food, dental toiletries, tobacco, drugs, etc.). Here, we use an integral approach including <i>ex vivo</i> experiments using a novel model of oral mucosa and saliva in well controlled conditions as well as <i>in vivo</i> dynamic instrumental and sensory experiments. <i>Ex vivo</i> experiments show the ability of the mucosal pellicle, the thin layer of salivary proteins covering the oral mucosa, to interact with aroma compounds, as well as the ability of oral cells and saliva to metabolize carbonyl aroma compounds. <i>In vivo</i> evaluation of the exhaled air and perception of individuals after aroma sample consumption confirm <i>ex vivo</i> findings in a more real context. Thus, aroma compounds susceptible to be metabolized by saliva and oral cells show a lower aroma persistence than non metabolized compounds, for which other mechanisms such as the adsorption at the surface of the oral mucosa (mucosal pellicle) as a function of their hydrophobicity are involved. Thus, we argue that the physiological aspects occurring during the oral processing, and especially, metabolization of aroma compounds, have to be considered when studying the phenomenon of aroma persistence.</p>

Abstract P242: Nicotinic Acetylcholine Receptor Subunit α7 is Protective Against Angiotensin II-induced Aneurysm and Hypertension

Hypertension ◽  
2017 ◽  
Vol 70 (suppl_1) ◽  
Author(s):  
Nayaab S Khan ◽  
Spyros Mavropoulos ◽  
Kaie Ojamaa
Keyword(s):  
Blood Pressure ◽  
Acetylcholine Receptor ◽  
Nicotinic Acetylcholine Receptor ◽  
Low Dose ◽  
Histological Analysis ◽  
Inflammatory Activity ◽  
High Dose ◽  
Ang Ii ◽  
Nicotinic Acetylcholine ◽  
Α7 Nachr

Alpha7 nicotinic acetylcholine receptor (α7 nAChR), an integral component of the cholinergic nervous system is known to mediate cholinergic anti-inflammatory activity in various disease models such as sepsis, stroke and neurocognitive disorders. We report for the first time that the α7 nAChR -/- deficient mouse serves as a novel model of hypertension and aneurysm formation. Seven month old male WT and α7 nAChR -/- mice weighing 28-33g were infused with low dose Ang II (350 ng/kg/min) or high dose (700 ng/kg/min) or vehicle for 15 days using mini-osmotic pumps (Alzet, model 2004) implanted subcutaneously. Blood pressure (BP) was recorded on day 0,3,7,10 and 14. Mice were euthanized on day 15. Heart and body weights were measured, histological analysis was performed on the aortas and immune profile of peripheral blood was analyzed by flow cytometry. High dose Ang II resulted in 70% mortality from aneurysm rupture in α7 nAChR -/- mice starting as early as the 4 th day of infusion. While cardiac hypertrophy was not observed, low dose Ang II resulted in a sharp rise in blood pressure in α7 nAChR -/- beginning on the 3 rd day to 167±3.7 mmHg compared to 138±3.3 mmHg in WT treated mice. On day14 of low dose treatment, BP in α7 nAChR -/- rose to 171±4.2 vs.135±3.1 in WT mice. No changes were observed in BP of untreated WT or α7 nAChR -/- animals. Histological analysis revealed high grade aneurysm in aortas of α7 nAChR -/- mice treated with low dose Ang II, demonstrating a prominent germinal center within the false lumen and fibrous desmoplastic stroma. Increased infiltration of CD11B + monocytes, and myeloperoxidase + stained neutrophils were observed in these aortas but not in the aortas of similarly treated WT mice. Flow cytometric analysis showed 27% ± 3.9 CD11B + /CD45 + circulating monocytes and 48% ± 0.8 Ly6G + /CD45 + neutrophils in α7 nAChR -/- vs. 19% ± 3 monocytes and 11.85% ± 2.9 neutrophils in WT mice. No differences in the levels of circulating immune cells were observed in untreated mice of either genotype. These data support a protective role of α7 nAChR in hypertension and aneurysm, potentially acting through its cholinergic anti-inflammatory activity. The α7 nAChR -/- mouse may serve as a new genetic model of aneurysm relevant in studies of the human disease.

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.

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.

Abstract 15751: A New Role of Sox6 in Renin Regulation

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Jose Gomez ◽  
Eric Sum ◽  
Anna Keyte ◽  
Conrad Hodgkinson ◽  
Mary Hutson ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Cell Fate ◽  
Kidney Development ◽  
Ex Vivo ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Renin Angiotensin System ◽  
Adult Kidney ◽  
Fold Reduction

Introduction: The renin-angiotensin system (RAS) is an important component of blood pressure regulation in mammals. Renin catalyzes the rate limiting step of RAS, is produced and stored by Juxtaglomerular (JG) cells in the kidney. However, the transcriptional mechanisms that govern the specification of renin expressing cells under normal or pathophysiological conditions remain poorly understood. During blood pressure changes the number of adult renal cells expressing renin increase through a process termed JG recruitment. We found that this process involves differentiation mesenchymal stromal-like cells (MSC) to renin expressing cells. Our aim in this study was to determine new regulators of renin cell fate during kidney development and JG recruitment. Methods: Gene expression profiles of MSC and JG cells were performed with Affymetrix Mouse 430 2.0 array. In vitro assays were performed in adult renal MSCs isolated from C57BL6 Ren1c YFP mice. Renin expression in vitro was induced by treatment with IBMX and Forskolin. MSC were transduced with lentivirus carrying vectors for Sox6, Sox6 shRNA or controls. Ex vivo analysis was performed in embryonic kidneys (14.5 dpc) isolated and transduced with Sox6 or scrambled shRNA, kidneys were then cultured for 4 days and the expression of Sox6 and Renin analyzed by IHC. Results: Data showed that the transcription factor Sox6 is expressed in renin producing cells in the developing kidney (n=4) and in the adult kidney after stimulation that promotes JG recruitment (n=3). Overexpression of Sox6 (n=3, P<0.05) enhanced differentiation of renal MSCs to renin producing cells in vitro , and Sox6 knockdown reduced differentiation of renal MSC to renin producing cells in vitro (6-fold, n=4, P<0.01). Furthermore, knockdown of Sox6 in an ex vivo model of kidney development resulted in a 5-fold reduction in renin expressing cells (n=4, P<0.05). Conclusion: These results support a novel role for Sox6 in the development of renin expressing cells. This may have implications for renal development and physiology, opening new possibilities of addressing questions regarding both developmental and physiological regulation of renin.

scholarly journals Long-term blood pressure lowering and cGMP-activating actions of the novel ANP analog MANP

2020 ◽  
Vol 318 (4) ◽  
pp. R669-R676 ◽  
Author(s):  
Yang Chen ◽  
Jacob J. Schaefer ◽  
Seethalakshmi R. Iyer ◽  
Gerald E. Harders ◽  
Shuchong Pan ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Subcutaneous Injection ◽  
Ex Vivo ◽  
Subcutaneous Administration ◽  
Therapeutic Drug ◽  
Hypertensive Rats ◽  
Pressure Lowering ◽  
Intracellular Ca ◽  
Isolated Arteries

Based on the cardiac hormone atrial natriuretic peptide (ANP) and its seminal role in blood pressure (BP) homeostasis, we investigated the chronic BP lowering actions of a novel ANP analog currently entering clinical trials for hypertension. Previous reports demonstrate that this analog MANP activates the guanylyl cyclase A receptor (GC-A) and results in more potent biological actions compared with ANP; thus, it may represent a new therapeutic drug for hypertension. A major goal of this study was to establish that chronic subcutaneous delivery of MANP is feasible and hypotensive together with cGMP effects. We investigated the BP-lowering and cGMP-activating actions of acute and chronic subcutaneous delivery in normal and hypertensive rats. Furthermore, we explored vascular mechanisms of MANP in human aortic smooth muscle cells (HASMC) and ex vivo in isolated arteries. In normal rats with a single subcutaneous injection, MANP promoted robust dose-dependent BP-lowering actions and natriuresis, together with cGMP activation. Most importantly in hypertensive rats, once-a-day subcutaneous injection of MANP for 7 days induced cGMP elevation and long-term BP reduction compared with vehicle. Mechanistically, in HASMC, MANP activated cGMP and attenuated angiotensin II-mediated increases in intracellular Ca2+ levels while directly vasorelaxing arterial rings. Our study demonstrates for the first time the effectiveness of subcutaneous administration of MANP for 7 days and provides innovative, vascular mechanisms of BP regulation supporting its continued development as a novel therapeutic for hypertension.

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