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Journal of Pharmacology And Experimental Therapeutics Fast Forward
First published on June 26, 2003; DOI: 10.1124/jpet.103.052670

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Received for publication April 7, 2003.
Revised May 7, 2003.
Accepted for publication June 10, 2003.

Temporal Effects of Stress by Immobilization and Sensitivity of the Isolated Rat Pacemaker to Isoproterenol: Roles of Corticosterone, Neuronal Uptake and {beta}-Adrenergic Homogeneity

Marco P. Brotto 1*

1 Case Western Reserve University

* Address correspondence to: E-mail: mab51{at}po.cwru.edu

Abstract

A number of diseases and pathological conditions are related to the long-term adaptive response to stress, in particular under conditions of chronic stress when allostasis can shift from a healthy toward a pathological state. While a vast number of studies have focused on the effects of chronic stress on brain and the immune system, fewer studies have been performed in peripheral tissues. Here we utilized the intact isolated right atrium (pacemaker) from the rat to investigate the temporal effects of stress induced by immobilization (restraint stress) on the sensitivity of the pacemaker to the chronotropic response to isoproterenol (i.e., the effect of isoproterenol to increase the frequency of contractions of pacemakers). Immobilization sessions were conducted at specific number of times (1, 3, 7, 9, 11, 14). We found that the response to stress over time approximates a Gaussian distribution (i.e., normal standard distribution) with no significant effects being detected after either 1 or 14 immobilization sessions, while supersensitivity to the chronotropic effect of ISO occurred after 3, 7, 9 and 11 immobilization sessions, with a peak effect occurring after 7 immobilization sessions. At a cellular level, we determined that both corticosterone and neuronal uptake of catecholamines were directly involved with the observed effects, while no alterations in the homogeneity of {beta}-adrenoceptors was detected in pacemakers of stressed animals. We hypothesize that these adaptations are essentially beneficial in nature, as they should allow the animals to more promptly respond to the demands imposed by the stressful conditions.


Key words: Corticosterone, Immobilization, Pacemaker, Rat, Stress, pA2


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