This thesis describes metabolic changes occurring in chromaffin cells when secreting catecholamine (principally adrenaline), and the factors involved in maintaining the rate of secretion. In perfused pig adrenal glands, <sup>31</sup/>p nuclear magnetic resonance showed that nucleotide stored with catecholamine in the secretory vesicles (chromaffin granules) of the chromaffin cell was distinguishable from cytoplasmic nucleotide. Intragranular pH was 5.52 ± 0.15 (± SD, n=8) in ischaemic glands and rose (+ 0.22 ± 0.16 (± SD, n=6)) on recovery of cytoplasmic ATP during perfusion. This suggests that catecholamine accumulation by the granules is not driven by an ATP-generated pH gradient in intact tissue, as cytoplasmic ATP did not reduce intragranular pH. Perfused cortex-free ox adrenal medulla consumed 0.51 ± 0.19 (± SD, n=8) μmole 0₂/min/g wet weight after 210-230 minutes of perfusion, and this rose 30% during 4 minute O.lmM acetylcholine stimulations. This enhancement correlated with secretion but depended on the mode of stimulation, indicating that ATP consumption in secretion itself was an inadequate explanation. The proton-translocating Mg-ATPase of the chromaffin granule may hydrolyse ATP at its uncoupled rate on entering the plasma membrane during secretion by exocytosis. 1.4 ± 0.9 (± SD, n=12) moles of catecholamine were secreted per mole of enhanced oxygen consumption over 16 minutes. From this ratio, the oxygen consumption enhancement is shown to be much larger than that predicted from uncoupled proton pumping. Ouabain-sensitive oxygen consumption rose from < 6% to 18 ± 8% (± SD, n=4) during prolonged acetylcholine stimulation in the absence of calcium, suggesting that Na,K-ATPase was not responsible for all of the oxygen consumption enhancement. On continuous stimulation, secretion showed a biphasic decline in both pig and ox. A decline was also observed on intermittent stimulation. Cell death, potential-sensitive calcium gating and acetylcholine receptor desensitisation were only minor contributors. Little recovery occurred on resting the tissue for 2-3 hours between stimulations. The results are explained in terms of depletion of a pool of chromaffin granules adjacent to the plasma membrane.

Thesis (Ph. D.)--University of Michigan, 1940. / Cover title. Thesis note on p. 709. "Reprinted from the American journal of physiology, vol. 129, no. 3, June, 1940." Bibliography: p. 723.

Thesis (Ph. D.)--University of Chicago, Committee on Neurobiology, June 2000. / Includes bibliographical references. Also available on the Internet.

Orexin A (or hypocretin 1)-immunoreactive neurons in the rat lateral hypothalamus project to several areas of the medulla oblongata that are closely associated with cardiovascular regulation. The present study was undertaken to further strengthen the hypothesis that orexin A accelerates cardiovascular response by activating sympathoexcitatory neurons in the rat rostral ventrolateral medulla (RVLM). First, immunohistochemical studies revealed the presence of orexin A-immunoreactive fibers in the RVLM. Double labeling the sections with orexin A- and tyrosine hydroxylase (TH)-antisera further showed that orexin A-immunoreactive fibers are in close proximity with TH-immunoreactive neurons, some of which may be barosensitive, bulbospinal neurons in the RVLM. Second, microinjection of orexin A (6.35, 12.7 and 38.1 μM) into the RVLM, which was verified later by histological examination, caused a significant increase of mean arterial pressure (MAP) and a moderate increase of heart rate (HR) in awake rats. L-glutamate (33.3 mM) injected into the same sites, caused a larger increase in MAP, but a decrease in HR; whereas, saline injection was without significant effect. Results from this study suggest that orexin A, which may be released from the nerve fibers originating from the neurons in the lateral hypothalamus, acting on RVLM neurons in the medulla, increases sympathetic outflow targeted to the heart and blood vessels in awake animals.

Fung Kwai Ching. / "August 2002." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2002. / Includes bibliographical references (p. 188-205). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.

The present study has established that physiological concentrations of estradiol can modulate stress-induced increases in plasma epinephrine (EPI). In anesthetized female rats, insulin-induced hypoglycemia (0.25 U/kg) increased plasma EPI concentration to a significantly greater extent in 14-day ovariectomized (OVEX) rats compared to sham-operated controls. In 17-estradiol (E2)-replaced OVEX rats, the hypoglycemia-induced rise in plasma EPI was significantly reduced compared to OVEX rats. This suppression was due to both decreased adrenal medullary output and increased clearance of EPI. Adrenal venous EPI concentration was significantly reduced in OVEX+E2 rats, suggesting that EPI secretion from the adrenalmedulla was decreased by E2 replacement. The underlying mechanism(s) of this apparent E2-mediated reduction in secretion could not be established since 1) the expression levels of the biosynthetic enzymes tyrosine hydroxylase and phenylethanolamine N-methyltransferase were not affected in OVEX+E2 rats, suggesting that EPI biosynthesis is similar in these and OVEX rats; and 2) agonist-induced increases in intracellular CaP2+P were identical in isolated adrenal medullary chromaffin cells exposed to E2 (10 nM) or vehicle for 48 hr, suggesting that stimulus secretion coupling is unaffected by E2 treatment. In contrast, plasma clearance of EPI was significantly increased in OVEX+E2 rats. Although 48 hr exposure to E2 had no effect on intracellular signaling in chromaffin cells, acute (3 min) exposure to micromolar concentrations of E2 dose-dependently and reversibly inhibited agonist-induced CaP 2+Ptransients. Consistent with this observation, acute (30 min) infusions of E2 also significantly reduced the insulin-induced increase in plasma EPI in OVEX rats. These data demonstrate that physiological levels of circulating E2 can modulate hypoglycemia-induced increases in plasma EPI. This effect appears to be mediated by the steroids influence on adrenal medullary EPI output and plasma EPI clearance; however the mechanism(s) underlying these E2-mediated modulations remain undetermined. This study has also established that acute exposure to supra-physiological levels of E2 can suppress hypoglycemia-induced increases in plasma EPI, due at least in part to inhibition of stimulus-secretion coupling.

Maintenance of a stable arterial blood pressure is a complex physiological phenomenon. In addition to dysfunction of the blood vessels, alterations in homeostasis of circulating signals and humoral factors also contribute significantly to the development of hypertension. Recent evidence indicates that accumulation of the byproducts of cellular respiration, including superoxide anion (O2-) and/or hydrogen peroxide (H2O2), are contributing factors in pathophysiology of hypertension. With respect to the central nervous system, neurons in the rostral ventrolateral medulla (RVLM) play a pivotal role in neural regulation of blood pressure. RVLM neurons not only provide a tonic excitation to maintain the sympathetic vasomotor activity of the blood vessels, they also participate in baroreceptor reflex control of blood pressure. The notion that production of O2- and/or H2O2 in the RVLM participates in central control of blood pressure has recently gained major recognition in the area of hypertension study. Nonetheless, detailed insights into the mechanisms underlying O2- and/or H2O2 promoted hypertension remain to be elucidated. The hypothesis that forms the basis of this study is that enhanced level of O2- and/or H2O2 in the RVLM may be important factors for the manifestation of hypertension in the spontaneously hypertensive rats (SHR), an animal model of human essential hypertension. In comparison to normotensive Wistar-Kyoto (WKY) rats, basal level of O2- in the RVLM region of adult male SHR rats was significantly higher, along with a reduction in the expression of superoxide dismutase 1 (SOD1), SOD2 or catalase. SOD and catalase are enzymes that metabolize cellular O2- or H2O2 respectively. Pharmacologically, microinjection bilaterally into the RVLM of SOD mimetic, Tempol (50 nmol) or a pan SOD/calatase mimetic, FeTMPyP (100 nmol), significantly decreased mean systemic arterial pressure (MSAP) or heart rate (HR) in both SHR and WKY rats. The maximal hypotensive effect produced by Tempol or FeTMPyP was significantly greater in SHR than WKY rats. We also found that in SHR, but not WKY rats, the hypotensive and bradycardiac responses after microinjection bilaterally into the RVLM of FeTMPyP was significantly greater than that by Tempol. In addition, infection of RVLM neurons with adenoviral vector encoding SOD1 (Ad-SOD1), SOD2 (Ad-SOD2) or catalase (Ad-Catalase) gene (5x108 pfu) into the bilateral RVLM resulted in a long-term hypotensive effect in SHR but not WKY rats. The temporal profile of Ad-catalase-promoted hypotension was again longer than that promoted by Ad-SOD1 or Ad-SOD2 alone. At the molecular level, gene transfer of SOD1, SOD2 or catalase into the RVLM region of SHR or WKY rats specifically increased the expression of individual protein, resulting in a reduction in O2- level. Together these results suggest that accumulation of O2- and/or H2O2 in the RVLM is involved in the neural mechanism of hypertension in SHR.

Photoreceptors in the eye basically provide information about light intensities from which brains extract different kinds of visual cues (e.g. color, movement, pattern). How do the properties and response characteristic of visual interneurons differ from the periphery to the central brain? I intracellularly recorded from neurons in the second and third optic ganglia (medulla and lobula) and the central brain (protocerebrum) of bees (mainly bumblebees; Bombus impatiens) while presenting color and motion stimuli. Bees rely on such stimuli during flight and foraging and show sophisticated visual learning abilities. We found that neurons in the distal medulla are color specific while ones in the proximal medulla show complex, often antagonistic color responses. Neurons in the distal lobula (layers 1-4) mainly process motion information while the proximal lobula (layers 5 and 6) seems to combine color and motion responses. Anterior parts of the central brain receive complex input representing combinations of motion and color information characterized by specific temporal properties (e.g. temporal precision, 'novelty' information or entrainment). This kind of often sparsely coded information is also represented in the mushroom bodies, learning and memory centers in the insect brain. In contrast, posterior parts of the central brain receive mainly motion information and show more reliable responses yet less precise spike timing. While the former kind of information (temporally precise or novelty in anterior pathways) is suited to form stimulus associations relevant during foraging, the latter, more reliable information is thought to support fast optomotor flight control maneuvers and other less plastic behaviors.

Thesis (M.S.)--University of Toledo, 2008. / "In partial fulfillment of the requirements for the degree of Master of Science in Biomedical Sciences." Title from title page of PDF document. Bibliography: p. 44-53, p. 77-90.

Thesis (Ph. D.)--University of Hong Kong, 1991.