Thesis Title

Age Attenuated Cutaneous Vasoconstrictor Response to Norepinephrine Is Apparent With Bretylium Tosylate

Date of Graduation

Spring 2007

Degree

Master of Science in Cell and Molecular Biology

Department

Biomedical Sciences

Committee Chair

Richard Garrad

Keywords

microdialysis, adrenergic blockade, dose-response, thermoregulation, bretylium tosylate

Subject Categories

Medical Molecular Biology

Abstract

The cutaneous vasoconstrictor response to cold is attenuated in older humans. The purpose of this study was to determine if an age associated decrease in cutaneous vasoconstriction is related to altered alpha-adrenergic responsiveness. Eight young (18 to 35 years of age) and eight older (55 to 75 years of age) subjects received seven doses (1.10⁻⁸ to 10⁻² log M) of norepinephrine delivered 2 æL min⁻¹) in lactated Ringer's solution by intradermal microdialysis at two sites, a control and bretylium pretreated. Skin blood flow was measured by laser-Doppler flowmetry and expressed as cutaneous vascular conductance (laser-Doppler flux/mean arterial blood pressure). The EC₅₀ of the dose response curves were similar between young and old subjects (EC₅₀ = -5.18±0.27 and -5.46±0.23 log M, respectively) in the control site. In the bretylium pretreated sites, the mean EC₅₀ was significantly greater in the older (-4.53±0.23 log M) compared to younger (-5.03±0.27 log M) subjects. These findings suggest when adrenergic release of norepinephrine is abolished with bretylium tosylate, age related attenuations in adrenergic vasoconstriction in the skin are uncovered. Additionally, it is likely the differences in presynaptic release of norepinephrine in young and older subjects may affect cutaneous vasconstrictor responsiveness to norepinephrine.

Copyright

© Daniel Skirrow Short

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Dissertation/Thesis

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