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• W2134617725 abstract "The adenosine A 1 receptor (A 1 R) inhibits β-adrenergic-induced contractile effects (antiadrenergic action), and the adenosine A 2A receptor (A 2A R) both opposes the A 1 R action and enhances contractility in the heart. This study investigated the A 1 R and A 2A R function in β-adrenergic-stimulated, isolated wild-type and A 2A R knockout murine hearts. Constant flow and pressure perfused preparations were employed, and the maximal rate of left ventricular pressure (LVP) development (+dp/d t max ) was used as an index of cardiac function. A 1 R activation with 2-chloro- N 6 -cyclopentyladenosine (CCPA) resulted in a 27% reduction in contractile response to the β-adrenergic agonist isoproterenol (ISO). Stimulation of A 2A R with 2- P(2-carboxyethyl)phenethyl-amino-5′- N-ethylcarboxyamidoadenosine (CGS-21680) attenuated this antiadrenergic effect, resulting in a partial (constant flow preparation) or complete (constant pressure preparation) restoration of the ISO contractile response. These effects of A 2A R were absent in knockout hearts. Up to 63% of the A 2A R influence was estimated to be mediated through its inhibition of the A 1 R antiadrenergic effect, with the remainder being the direct contractile effect. Further experiments examined the effects of A 2A R activation and associated vasodilation with low-flow ischemia in the absence of β-adrenergic stimulation. A 2A R activation reduced by 5% the depression of contractile function caused by the flow reduction and also increased contractile performance over a wide range of perfusion flows. This effect was prevented by the A 2A R antagonist 4-(2-[7-amino-2-(2-furyl)[1,2,4]triazolo[2,3-a][1,3,5]triazin-5-ylamino]ethyl)phenol (ZM-241385). It is concluded that in the murine heart, A 1 R and A 2A R modulate the response to β-adrenergic stimulation with A 2A R, attenuating the effects of A 1 R and also increasing contractility directly. In addition, A 2A R supports myocardial contractility in a setting of low-flow ischemia." @default.
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• W2134617725 date "2006-01-01" @default.
• W2134617725 modified "2023-10-11" @default.
• W2134617725 title "Contractile effects of adenosine A₁ and A_2A receptors in isolated murine hearts" @default.
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• W2134617725 doi "https://doi.org/10.1152/ajpheart.00740.2005" @default.
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