Effect of high salt diet on blood vessel function: alteration in vascular β-adrenoceptor signalling

Mahajan, Puneet (2012) Effect of high salt diet on blood vessel function: alteration in vascular β-adrenoceptor signalling. Doctoral (PhD) thesis, Memorial University of Newfoundland.

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    Available under License - The author retains copyright ownership and moral rights in this thesis. Neither the thesis nor substantial extracts from it may be printed or otherwise reproduced without the author's permission.
    (Original Version)

Abstract

Consumption of high salt leads to the alteration of vascular β-adrenoceptor response which subsequently modifies the blood vessel responses. This change could be due to an alteration in β-adrenoceptor-mediated signalling in blood vessels. To test this hypothesis, an evaluation of β-adrenoceptor-mediated mechanical and electrical responses was undertaken in low-pressure segment of the circulatory system i.e. main pulmonary arteries, of Sprague-Dawley rats fed either normal or high salt diets for 18-23 days. Blood pressure and heart rate were monitored in anesthetised rats using infra-arterial catheters. Isometric tension was measured in isolated pulmonary artery ring preparations. Glass microelectrodes were used for the recording of membrane potential (Em). -- Consumption of high salt resulted in a modest increase in blood pressure but not heart rate. Isoprenaline evoked hyperpolarization in pulmonary arteries of rats fed a normal diet. Hyperpolarization evoked by stimulation of β-adrenoceptor involved multiple processes including the activation of K + channels and Na+ /K+ATPase. -- The removal of endothelium produced hyperpolarization of vascular smooth muscle cells in blood vesselsobtained from rats fed a normal diet. The hyperpolarisation due to denudation was the result of the activationof K+ channels and Na+ /K+ ATPase. Moreover, hyperpolarization as a consequence of β-adrenoceptor stimulation appeared to be mutually dependent on the presence of endothelial cells since this event (i.e. hyperpolarization) as evoked by isoprenaline was absent in denuded tissues. Isoprenaline-mediated relaxation was found to be partly dependent on the presence of endothelium. -- Isoprenaline produced similar relaxations in intact pulmonary arteries obtained from animals fed a high saltcompared to normal diet. However, the Em was found to be more negative in intact pulmonary arteries ofanimals fed a high salt diet compared to those fed a normal diet. The isoprenaline evoked hyperpolarization was notably absent in the pulmonary arteries. In addition, in intact versus denuded blood vessels obtained from rats on high salt diet, the Em was not significantly different. -- Taken together, the data suggests that the presence of the endothelium is essential for the propagation of β-adrenoceptor-mediated relaxation. Moreover, the evidence seems to also imply that consumption of high saltleads to the activation of K+ channels and Na+ /K+ ATPase channels preserving β-adrenoceptor-mediated relaxations in pulmonary arteries.

Item Type: Thesis (Doctoral (PhD))
URI: http://research.library.mun.ca/id/eprint/6147
Item ID: 6147
Additional Information: Includes bibliographical references (leaves 142-168).
Department(s): Medicine, Faculty of
Date: 2012
Date Type: Submission
Library of Congress Subject Heading: Vascular endothelium; Sodium/potassium ATPase; Sodium--Metabolism; Beta adrenoceptors;
Medical Subject Heading: Endothelium, Vascular; Sodium, Dietary--metabolism; Sodium-Potassium-Exchanging ATPase;

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