Antihypertensive mechanisms of metformin.
Item
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Title
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Antihypertensive mechanisms of metformin.
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Identifier
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AAI9969713
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identifier
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9969713
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Creator
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Morales, J. C.
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Contributor
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Adviser: Martin S. Muntzel
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Date
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2000
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Language
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English
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Publisher
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City University of New York.
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Subject
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Biology, Neuroscience | Biology, Animal Physiology | Health Sciences, Pharmacology
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Abstract
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The present body of literature on metformin provides evidence that acute metformin lowers blood pressure levels through sympathetic withdrawal and lowered vascular reactivity, it is unclear that these findings can be extrapolated to explain the observed hypotension reported during chronic treatment. In addition, no previous study has examined the possibility that metformin may simultaneously reduce sympathetic neural flow and vascular reactivity.;This study addresses whether long-term metformin treatment decreases blood pressure by decreasing sympathetic nerve activity and/or vascular smooth muscle reactivity.;The first section of this study assessed the influence of long-term treatment of metformin on the sympathetic nerve activity, specifically norepinephrine (NE), epinephrine (Epi) and dopamine (DA) were measured. NE plasma concentrations were lowered in metformin rats. However, Epi concentrations in plasma were increased by metformin treatment.;The second section of this study assessed sympathetic nerve activity involvement by quantifying the fall in blood pressure produced by ganglionic blockade. Metformin slightly but not significantly reduced the fall in BP to Hex indicating a reduction in sympathetic nerve activity.;The third section of this study assessed vascular contractility to pressor agents in rats that have been chronically treated with metformin. In this section, it was found that metformin increased the vascular reactivity to both phenylephrine and angiotensin II.;In summary, metformin lowered NE spill-over release but increased Epi spill-over release. In addition, metformin tended cause an attenuated fall in blood pressure in response to Hexamethomium bromide. Surprisingly, metformin caused an increase in blood pressure reactivity to both phenylephrine and angiotensin II. Phenylephrine and angiotensin II caused expected changes in regional blood flow, however, no differences were observed between the metformin and control groups. In conclusion, metformin caused a chronic decrease in BP that was caused by a decrease in sympathetic nerve activity, but was not secondary to a decrease in vascular reactivity. In fact, we observed an increase in vascular reactivity in metformin treated rats.
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Type
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dissertation
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Source
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PQT Legacy CUNY.xlsx
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degree
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Ph.D.
