Functional β₂-adrenoceptors in rat left atria: effect of foot-shock stress

Abstract

Altered sensitivity to the chronotropic effect of catecholamines and a reduction in the β/β-adrenoceptor ratio have previously been reported in right atria of stressed rats, human failing heart, and aging. In this report, we investigated whether left atrial inotropism was affected by foot-shock stress. Male rats were submitted to 3 foot-shock sessions and the left atrial inotropic response, adenylyl cyclase activity, and β-adrenoceptor expression were investigated. Left atria of stressed rats were supersensitive to isoprenaline when compared with control rats and this effect was abolished by ICI118,551, a selective β-receptor antagonist. Schild plot slopes for the antagonism between CGP20712A (a selective β-receptor antagonist) and isoprenaline differed from unity in atria of stressed but not control rats. Atrial sensitivity to norepinephrine, as well as basal and forskolin- or isoprenaline-stimulated adenylyl cyclase activities were not altered by stress. The effect of isoprenaline on adenylyl cyclase stimulation was partially blocked by ICI118,551 in atrial membranes of stressed rats. These findings indicate that foot-shock stress equally affects inotropism and chronotropism and that β-adrenoceptor upregulation contributes to the enhanced inotropic response to isoprenaline.

Enhanced beta-1 adrenergic receptor responsiveness in coronary arterioles following intravenous stromal vascular fraction therapy in aged rats

“…However, we did not find a significant difference in vasodilation between the groups using the selective β2-AR agonist, salbutamol (Fig 3B). While β2: β1-AR ratio increases in failing human hearts [32] and in senescent hearts [3,52], we have a novel observation that the opposite occurs in β2-AR staining in arterioles from OC, and this wasn’t altered with SVF treatment (Fig 6).…”

Stress-induced Differential Gene Expression in Cardiac Tissue

“…Therefore, in the heart of untreated stressed rats, the downregulation of β 1 -AR and apelin seems to be counterbalanced by the upregulation of β 2 -AR and the action of CREM and RGS2. Therefore, although the proportion of β-AR subtypes is altered, there is no difference in cAMP formation by left atrial membranes of control and foot shock stressed rats stimulated by β 1 /β 2 -AR non-selective agonists [13]. However, when the membranes are stimulated in the presence of the β 2 -AR antagonist (ICI118,551), the amount of cAMP synthetized by the atrial membranes of stressed rats is lower than that of unstressed ones [13].…”

“…Therefore, although the proportion of β-AR subtypes is altered, there is no difference in cAMP formation by left atrial membranes of control and foot shock stressed rats stimulated by β 1 /β 2 -AR non-selective agonists [13]. However, when the membranes are stimulated in the presence of the β 2 -AR antagonist (ICI118,551), the amount of cAMP synthetized by the atrial membranes of stressed rats is lower than that of unstressed ones [13]. This is probably because the increase in the expression of CREM is not su cient to sustain the synthesis of cAMP, since β 1 -AR is downregulated, as has been reported elsewhere [13].…”

“…Since β 2 -AR is upregulated in the heart of stressed rats [13,21], its in uence on target genes expression under stress was also evaluated in the heart of rats treated with ICI (with or without stress).…”

“…These effects of stress were cancelled in the presence of selective β 2 -AR antagonists or non-selective β-AR antagonists, suggesting an increase in the β 2 -AR subtype in the cardiac tissue [10,13,15,16]. A Western blot approach con rmed the higher expression of β 2 -AR accompanied by a low expression of β 1 -AR in the atrium and ventricle of rats submitted to foot shock stress when compared to control non-stressed rats [13]. A reduced cardiac β 1 /β 2 -AR ratio is also involved in other circumstances, such as aging and heart failure.…”