Changes In Central And Peripheral Regulation Of Streptozotocin-Induced Diabetic Rats
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Date
2012-04
Authors
Hassan, Zurina
Journal Title
Journal ISSN
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Publisher
Universiti Sains Malaysia
Abstract
Alterations of cardiovascular reflexes in diabetes contribute to the increased cardiovascular morbidity and mortality. These alterations may be mediated at the level of afferent nerves, central baroreflex or efferent nerves within the baroreflex circuitry. Using the streptozotocin (STZ)-induced diabetic rats, the current study was designed to: (1) examine systematically diabetes-induced alteration of the multiple neural components by investigating the afferent nerves of the baroreceptor reflex, contribution of the central baroreflex in the rostral ventrolateral medulla (RVLM) and paraventricular nucleus (PVN) and distribution of activated neurons (c-Fos) in response to baroreceptor activation; (2) evaluate the vascular responsiveness of the diabetic pithed rats in the absence of baroreflex; and (3) examine the potential cellular mechanisms in isolated in vitro aortic rings that may contribute to vascular dysfunction. Results of baroreceptor reflex in STZ-induced diabetic rats showed baroreflex-mediated bradycardia was decreased in phenylephrine (PE)-induced increases in arterial pressure whereas reflex tachycardia was preserved in sodium nitroprusside (SNP)-induced decreases in arterial pressure. To test for the contribution of central baroreflex, microinjection of L-glutamate (1nmol in 100nL) showed sympathoexcitation. Meanwhile, microinjection with GABA (50nM in 100nL) showed sympathoinhibition in the RVLM regions. However, the results obtained did not show any difference between both groups and this was in line with the result of c-Fos immunohistochemistry, which demonstrated that the number of activated neurons in the NTS and RVLM was similar. It is evident that the damage was not due to baroreceptor sensory nerves. In addition, the pharmacological stimulation of glutamatergic neurons with DL-Homocysteic acid (200mM in 100nL) in the PVN region showed a significant depression in both MAP and HR of diabetic rats as observed in to bicuculline methiodide (GABAA receptor antagonist, 1mM in 100nL), but not to muscimol hydrobromide (GABAA receptor agonist, 2mM in 100nL). These results are suggestive of the attenuation of GABAergic tonic inhibitory action on glutamatergic sympathoexcitation.
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Keywords
Alterations of cardiovascular reflexes in diabetes , cardiovascular morbidity and mortality