No description available.

The system involved in mechanotransduction by proprioceptive sensory organs, such as muscle spindles, is poorly understood. We previously reported that stretch releases glutamate from synaptic-like vesicles (SLVs) within muscle spindle terminals (the proprioceptive sensory organs of muscles), and activates a non-canonical mGluR, modulating afferent firing (Bewick et al, 2005). If, as our previous data and the literature suggests, this system is present in other mechanosensory endings, such as baroreceptors, it presents a drugable target in the treatment of hypertension. With current hypertension therapy ineffective in around 20% of patients a novel target such as this is highly important to investigate. This study aimed to further investigate this receptor's pharmacology by screening ligands selective for classical mGluRs for their ability to alter stretch-evoked spindle firing in muscle spindles and SLV uptake in lanceolate endings. I found that although there are differences between the two systems, overall the pharmacology most closely matches that of the currently unsequenced phospholipase D coupled mGluR previously studied in the hippocampus (Pellegrini-Giampietro et al., 1996). Furthermore the pharmacology does not match that of any canonical mGluR (or iGluR). This pharmacological profiling allowed the development of novel kainate-derived compounds which were tested to find more potent analogues suitable for “click chemistry” (Kolb et al, 2001). The development of these compounds allowed further compounds to be synthesised with biotin and fluorescent side chains which will be used in further studies ultimately to allow sequencing of the receptor. In respect to baroreceptors I expanded our data in the working-heart-brainstem model and developed an isolated aortic preparation which will be used in further studies to further characterise this SLV/glutamate system in baroreceptors.

No description available.

Thesis (Ph.D.)--Ohio University, August, 2005. / Includes bibliographical references (leaves 156-175)

No description available.

The present study documents that baroreceptors located in the pulmocutaneous artery (PCA) are key components in control of lymph heart rate in amphibians. A negative feedback control loop exists between arterial pressure and lymphatic heart rate. The recurrent laryngeal nerve (rLN), which innervates the PCA baroreceptors, transmits information on arterial pressure to integration centers in the central nervous system. Lymphatic heart rate (LHR) is reduced as a result of increases in arterial pressure. This loop was determined using three experimental protocols. First, the correlation between LHR reduction and hormonally induced vasoconstriction was determined. Increases in arterial pressure due to pressor actions of angiotensin II and arginine vasotocin at high concentrations was negatively correlated to LHR. Second, lymphatic heart rate changes due to natural increases in arterial pressure were compared to rate changes due to increase in arterial pressure after bilateral denervation of the rLN. Post-denervation LHR was not affected by natural increase in arterial pressure prior to the establishment of a new resting arterial pressure. Increase in arterial pressure due to administration of vasoconstricting hormones was negatively correlated with LHR following denervation. Third, the effect on LHR due to direct stimulation of the rLN was studied. Stimulation of the rLN caused LHR to stop without increases in arterial pressure. Presumably, this negative feedback loop is present to limit fluid return to the cardiovascular system from the lymphatic system during periods of acute hypertension. Reduction in the return of lymph volume to the cardiovascular system could eliminate potential damage to pulmonary tissues due to high arterial pressures.

Thesis (Ph. D.)--University of Missouri--Columbia, 2002. / Typescript. Vita. Includes bibliographical references (leaves 121-148). Also issued on the Internet.

No presente trabalho investigamos em ratos hipertensos espontâneos (SHR) e seus controles normotensos (WKY) os efeitos do treinamento físico sobre a atividade simpática a diferentes territórios, bem como os efeitos da remoção seletiva dos baroreceptores arteriais sobre a atividade simpática. SHR e WKY foram submetidos à desnervação sino-aórtica (SAD) ou cirurgia fictícia (SHAM) e alocados aos grupos T (50-60% da capacidade máxima, 1 hora/dia, 5 dias/semana) ou mantidos sedentários (S) por 3 meses.Nossos dados demonstraram que as adaptações induzidas pelo T no simpático periférico são tecido-específicos e dependem da linhagem experimental: redução do simpático ao coração e rins de WKY e SHR, com redução da atividade simpática ao músculo esquelético nos WKY treinados, mas aumentado nos SHR treinados, os quais apresentam simultaneamente extenso remodelamento vascular. Nossos dados demonstraram ainda, que as adaptações do simpático induzidas pelo T dependem da integridade dos baroreceptores arteriais. / In the present study we investigate in spontaneous hypertensive rats (SHR) and their normotensive controls (WKY) the effects of exercise training on sympathetic activity to different territories and the effects of the selective removal of arterial baroreceptors on sympathetic activity. SHR and WKY were subjected to sinoaortic denervation (SAD) or sham surgery (SHAM) and submitted to T (50-60% of maximum capacity, 1 hour / day, 5 days/week) or kept sedentary (S) for 3 months.Our data demonstrated that T-induced changes in peripheral sympathetic innervations are tissue-specific and depend on the experimental strain: reduced sympathetic to the heart and kidneys in WKY and SHR strains, and reduced sympathetic activity to the skeletal muscles in the trained WKY, but increased sympathetic activity in the trained SHR, which showed a simultaneous extensive vascular remodeling after training. Our results also demonstrated that training-induced sympathetic adaptations depend on the integrity of the arterial baroreceptors.

壓力感受器在調節血壓的壓力感受性反射中的作用已是眾所周知。兩個動脈壓力感受器，分別為主動脈壓力感受器和頸動脈壓力感受器。它們作為重要的感應器以檢測主要動脈血壓，並和孤束核溝通，從而調節血壓。然而，壓力感受器的機械力敏感元件的分子身份仍是奧秘。因為機械敏感的陽離子通道受機械力刺激時會增加的神經元活動, 所以機械敏感的陽離子通道是合適的候選人。 / 在本研究中，通過使用膜片鉗和動作電位的測量，瞬时受体电位通道C5(TRPC5)被確定在主動脈壓力感受器的機械傳感器中。透過在壓力感受器神經元的鈣測量實驗，證實TRPC5參與由拉伸引起的鈣離子([Ca²⁺]i)上升。TRPC5基因敲除小鼠出現壓力感受器功能受損, 表明了TRPC5在血壓控制的重要性。 / 比較主動脈壓力感受器或頸動脈壓力感受器的不同敏感度現時存有不少爭論。在本研究中，我發現主動脈壓力感受器比頸動脈壓力感受器對於壓力變化更加敏感。此外，我還發現了主動脈壓力感受器神經元比頸動脈壓力感受器神經元有一個相對較高的瞬时受体电位通道V4(TRPV4)表達。鈣測量研究表明TRPV4通道在主動脈壓力感受器神經元的靈敏度可能發揮著重要作用。 / Baroreceptors have been well known for its role in the baroreflex regulation of blood pressure. Two arterial baroreceptors, aortic and carotid baroreceptors, serve as the important sensors to detect blood pressure in main arteries, and they communicate with the solitary nucleus tract for blood pressure regulation. However, the molecular identity of the mechano-sensitive components in the baroreceptors is still mysteries. Mechano-sensitive cation channels are the fascinating candidates as they increase neuronal activities when stimulated by stretch. In the present study, with the use of patch clamp and action potential measurement, TRPC5 channels were identified to be the mechanical sensor in the aortic baroreceptor. Calcium measurement studies demonstrated that TRPC5 was involved in the stretch-induced [Ca2+]i rise in baroreceptor neurons. The importance of TRPC5 in blood pressure control was also studied in TRPC5 knockout mice, which displayed an impaired baroreceptor function. / There have been controversies as to whether aortic baroreceptors or carotid baroreceptors are more sensitive to the change in blood pressure. In the present study, aortic baroreceptor was found to be more sensitive to the pressure change than the carotid baroreceptor. Furthermore, I also found a relative higher expression of TRPV4, a mechanosensitive channel, in the aortic baroreceptor neurons than in the carotid baroreceptor neurons. Moreover, calcium measurement studies showed that TRPV4 channels should play an important role in governing the differential pressure sensitivity in these two types of baroreceptor neurons. / Taken together, the present study provided novel information on the role of TRPC5 and TRPV4 in baroreceptor mechanosensing. In future, it will be of interest to explore whether TRPC5 and/or TRPV4 dysfunction could contribute to human diseases that are related to blood pressure control. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Lau, On Chai Eva. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2013. / Includes bibliographical references (leaves 133-152). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts also in Chinese. / Declaration --- p.i / Abstract of the thesis entitled --- p.ii / Acknowledgement --- p.vii / Abbreviation --- p.ix / Table of content --- p.xii / List of figures --- p.xv / List of table --- p.xvii / Chapter Chapter 1: --- Introduction --- p.1 / Chapter 1.1 --- Baroreceptors --- p.1 / Chapter 1.1.2 --- Arterial baroreceptors --- p.2 / Chapter 1.1.2.1 --- Functions of arterial baroreceptors --- p.4 / Chapter 1.1.2.2 --- Sensitivity of the arterial baroreceptors --- p.6 / Chapter 1.1.3 --- Other baroreceptors --- p.8 / Chapter 1.1.4 --- The molecular identity of the mechanosensors in baroreceptor neurons --- p.9 / Chapter 1.2 --- Transient receptor potential ion channels (TRP channels) --- p.10 / Chapter 1.2.1 --- TRP channels superfamily --- p.10 / Chapter 1.2.2 --- Multimerization of TRP channels --- p.12 / Chapter 1.2.3 --- Physiological functions --- p.14 / Chapter 1.2.4 --- Mechanosensitive TRP channels --- p.16 / Chapter 1.2.5 --- Canonical transient receptor potential 5 (TRPC5) channels --- p.17 / Chapter 1.2.6 --- Vanilloid transient receptor potential 4 (TRPV4) channels Figures --- p.20 / Chapter Chapter 2: --- Objectives --- p.34 / Chapter Chapter 3: --- Materials and Methods --- p.35 / Chapter 3.1 --- Materials --- p.35 / Chapter 3.1.1 --- Chemicals and reagents --- p.35 / Chapter 3.1.2 --- Solutions --- p.36 / Chapter 3.1.2.1 --- Solutions for calcium imaging --- p.36 / Chapter 3.1.2.2 --- Solutions for electrophysiology study --- p.38 / Chapter 3.1.2.3 --- Solutions for agarose gel electrophoresis --- p.41 / Chapter 3.1.3 --- Primers for RT-PCR --- p.42 / Chapter 3.1.4 --- Animals --- p.43 / Chapter 3.2 --- Methods --- p.43 / Chapter 3.2.1 --- Total RNA isolation and RT-PCR --- p.43 / Chapter 3.2.2 --- Immunohistochemistry --- p.44 / Chapter 3.2.3 --- Neuron labeling by DiI --- p.45 / Chapter 3.2.4 --- Neuron culture --- p.46 / Chapter 3.2.5 --- [Ca²⁺]i measurement --- p.47 / Chapter 3.2.6 --- Electrophysiology --- p.48 / Chapter 3.2.7 --- Evaluation of baroreflex response --- p.49 / Chapter 3.2.8 --- Telemetric measurement of blood pressure --- p.50 / Chapter 3.2.9 --- Statistical analysis --- p.51 / Figures --- p.52 / Chapter Chapter 4: --- Functional role of TRPC5 channels in aortic baroreceptor --- p.56 / Chapter 4.1 --- Introduction --- p.56 / Chapter 4.2 --- Materials and Methods --- p.59 / Chapter 4.2.1 --- Animals --- p.59 / Chapter 4.2.2 --- Immunohistochemistry --- p.59 / Chapter 4.2.3 --- Neuron labeling by DiI --- p.61 / Chapter 4.2.4 --- Neuron culture --- p.62 / Chapter 4.2.5 --- [Ca²⁺]i measurement --- p.63 / Chapter 4.2.6 --- Electrophysiology --- p.63 / Chapter 4.2.7 --- Evaluation of baroreflex response --- p.64 / Chapter 4.2.8 --- Telemetric measurement of blood pressure --- p.66 / Chapter 4.2.9 --- Statistical analysis --- p.67 / Chapter 4.3 --- Results --- p.67 / Chapter 4.3.1 --- Endogenous expression of TRPC5 channels in aortic baroreceptor neurons --- p.67 / Chapter 4.3.2 --- Characterization on the pressure-sensitive component in aortic baroreceptors --- p.68 / Chapter 4.3.3 --- Involvement of TRPC5 in [Ca²⁺]i response in aortic baroreceptor neurons --- p.69 / Chapter 4.3.4 --- Participation of TRPC5 in pressure-induced action potential firing in cultured aortic baroreceptor neurons --- p.70 / Chapter 4.3.5 --- Role of TRPC5 in baroreceptor sensory nerve activity and baroreflex regulation --- p.71 / Chapter 4.3.6 --- Importance of TRPC5 in baroreceptor function --- p.72 / Chapter 4.4 --- Discussions --- p.74 / Figures --- p.79 / Table --- p.98 / Chapter Chapter --- 5: TRPV4 channels and baroreceptor sensitivity --- p.99 / Chapter 5.1 --- Introduction --- p.99 / Chapter 5.2 --- Materials and Methods --- p.101 / Chapter 5.2.1 --- Animals --- p.101 / Chapter 5.2.2 --- Neuron labeling by DiI --- p.101 / Chapter 5.2.3 --- Neuron culture --- p.102 / Chapter 5.2.4 --- Electrophysiology --- p.103 / Chapter 5.2.5 --- Immunohistochemistry --- p.104 / Chapter 5.2.6 --- [Ca²⁺]i measurement --- p.105 / Chapter 5.2.7 --- Statistical analysis --- p.105 / Chapter 5.3 --- Results --- p.106 / Chapter 5.3.1 --- Properties of the aortic and carotid baroreceptor neurons --- p.106 / Chapter 5.3.2 --- Stretch sensitivity of aortic and carotid baroreceptor neurons --- p.108 / Chapter 5.3.3 --- mRNA expression of mechanosensitive TRP channels in aortic and carotid baroreceptor neurons --- p.109 / Chapter 5.3.4 --- Protein expression of TRPV4 channels in aortic and carotid baroreceptor neurons --- p.109 / Chapter 5.3.5 --- Involvement of TRPV4 in stretch-induced [Ca²⁺]i response in baroreceptor neurons --- p.110 / Chapter 5.4 --- Discussions --- p.111 / Figures --- p.116 / Chapter Chapter 6: --- General conclusions and future directions --- p.124 / Figures --- p.128 / References --- p.133

Thesis (Ph. D.)--University of Missouri--Columbia, 2000. / Typescript. Vita. Includes bibliographical references (leaves 166-187). Also available on the Internet.