Sole activation of three luminal adenosine receptor subtypes in different parts of coronary vasculature

Rafael Rubio; Guillermo Ceballos

doi:10.1152/ajpheart.00068.2002

Sole activation of three luminal adenosine receptor subtypes in different parts of coronary vasculature

Rafael Rubio, Guillermo Ceballos

Escuela Superior de Medicina (ESM)

Research output: Contribution to journal › Article › peer-review

17 Scopus citations

Abstract

In isolated guinea pig hearts saline perfused at constant flow, adenosine A₁, A_2A, and A₃ (A_x) agonists covalently bound to a large polymer (Pol; ≫2,000 kDa) were intracoronarily administered, and three effects were studied: dromotropic, vascular and inotropic. The rank order of potencies were the following: dromotropic (Pol-A_2A≪≪Pol-A₁>Pol-A₃) and vascular and inotropic (Pol-A_2A≥Pol-A₁≫Pol-A₃), where the rank order of potency for Pol-A_x depends on the part of the coronary vascular network involved; i.e., there is a vascular heterogeneity. The large size of Pol-A_x prevents extravascular diffusion and causes it to act solely in the endothelial luminal surface. This implies their cardiac effects are due to endothelial mediators. Inhibition of nitric oxide (NO) and prostaglandin (PG) synthesis with N^G-nitro-L-arginine methyl ester and indomethacin, respectively, show that the three cardiac effects of Pol-A₁ were mediated by NO and PG, whereas for Pol-A_2A and Pol-A₃ the mediator was mainly NO but not PG. These results suggest that if Pol-A_x activated the corresponding endothelial A_x-receptor subtype, a different mediator would be produced.

Original language	English
Pages (from-to)	H204-H214
Journal	American Journal of Physiology - Heart and Circulatory Physiology
Volume	284
Issue number	1 53-1
DOIs	https://doi.org/10.1152/ajpheart.00068.2002
State	Published - 1 Jan 2003

Keywords

Cardiac function control
Endothelial control
Endothelial heterogeneity
Endothelial mediators
Luminal endothelial receptors
Parenchymal function modulation

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10.1152/ajpheart.00068.2002

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abstract = "In isolated guinea pig hearts saline perfused at constant flow, adenosine A1, A2A, and A3 (Ax) agonists covalently bound to a large polymer (Pol; ≫2,000 kDa) were intracoronarily administered, and three effects were studied: dromotropic, vascular and inotropic. The rank order of potencies were the following: dromotropic (Pol-A2A≪≪Pol-A1>Pol-A3) and vascular and inotropic (Pol-A2A≥Pol-A1≫Pol-A3), where the rank order of potency for Pol-Ax depends on the part of the coronary vascular network involved; i.e., there is a vascular heterogeneity. The large size of Pol-Ax prevents extravascular diffusion and causes it to act solely in the endothelial luminal surface. This implies their cardiac effects are due to endothelial mediators. Inhibition of nitric oxide (NO) and prostaglandin (PG) synthesis with NG-nitro-L-arginine methyl ester and indomethacin, respectively, show that the three cardiac effects of Pol-A1 were mediated by NO and PG, whereas for Pol-A2A and Pol-A3 the mediator was mainly NO but not PG. These results suggest that if Pol-Ax activated the corresponding endothelial Ax-receptor subtype, a different mediator would be produced.",

keywords = "Cardiac function control, Endothelial control, Endothelial heterogeneity, Endothelial mediators, Luminal endothelial receptors, Parenchymal function modulation",

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AB - In isolated guinea pig hearts saline perfused at constant flow, adenosine A1, A2A, and A3 (Ax) agonists covalently bound to a large polymer (Pol; ≫2,000 kDa) were intracoronarily administered, and three effects were studied: dromotropic, vascular and inotropic. The rank order of potencies were the following: dromotropic (Pol-A2A≪≪Pol-A1>Pol-A3) and vascular and inotropic (Pol-A2A≥Pol-A1≫Pol-A3), where the rank order of potency for Pol-Ax depends on the part of the coronary vascular network involved; i.e., there is a vascular heterogeneity. The large size of Pol-Ax prevents extravascular diffusion and causes it to act solely in the endothelial luminal surface. This implies their cardiac effects are due to endothelial mediators. Inhibition of nitric oxide (NO) and prostaglandin (PG) synthesis with NG-nitro-L-arginine methyl ester and indomethacin, respectively, show that the three cardiac effects of Pol-A1 were mediated by NO and PG, whereas for Pol-A2A and Pol-A3 the mediator was mainly NO but not PG. These results suggest that if Pol-Ax activated the corresponding endothelial Ax-receptor subtype, a different mediator would be produced.

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KW - Parenchymal function modulation

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Sole activation of three luminal adenosine receptor subtypes in different parts of coronary vasculature

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Keywords

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