Functional characterization of coronary vascular adenosine receptors in the mouse

• Published in: British journal of pharmacology Vol. 133; no. 7; pp. 1063 - 1072
• Main Authors: Flood, Amanda, Headrick, John P
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.08.2001; Nature Publishing
• Subjects: 2-Chloroadenosine - pharmacology; Adenosine; Adenosine - analogs & derivatives; Adenosine - pharmacology; Adenosine Triphosphate - physiology; Adenosine-5'-(N-ethylcarboxamide) - pharmacology; Animals; Biological and medical sciences; Blood vessels and receptors; coronary; Coronary Vessels - drug effects; Coronary Vessels - physiology; Dose-Response Relationship, Drug; Enzyme Inhibitors - pharmacology; Fundamental and applied biological sciences. Psychology; Glyburide - pharmacology; Heart - drug effects; Heart - physiology; In Vitro Techniques; Male; Mice; Mice, Inbred C57BL; mouse; Nitric Oxide Synthase - antagonists & inhibitors; Nitroarginine - pharmacology; Phenethylamines - pharmacology; Potassium Channel Blockers; Purinergic P1 Receptor Agonists; rat; Rats; Rats, Wistar; receptor; Receptors, Purinergic P1 - physiology; Vascular Resistance - drug effects; vasodilatation; Vasodilation - drug effects; Vasodilator Agents - pharmacology; Vertebrates: cardiovascular system; Heart; Agonist; Molecular form; Rat; Interspecific comparison; Rodentia; Coronary artery; Smooth muscle; Ionic channel; In vitro; Biological activity; Vasodilation; Muscular relaxation; Vertebrata; Mammalia; Vascular resistance; Mouse; Animal; Nitric oxide; Blood vessel; Circulatory system; Adenosine receptor; Potassium
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1038/sj.bjp.0704170

Coronary responses to adenosine agonists were assessed in perfused mouse and rat hearts. The roles of nitric oxide (NO) and ATP‐dependent K+ channels (KATP) were studied in the mouse. Resting coronary resistance was lower in mouse vs rat, as was minimal resistance (2.2±0.1 vs 3.8±0.2 mmHg ml−1 min−1 g−1). Peak hyperaemic flow after 20–60 s occlusion was greater in mouse. Adenosine agonists induced coronary dilation in mouse, with pEC50s of 9.4±0.1 for 2‐[p‐(2‐carboxyethyl)phenethylamino]‐5′‐N‐ethyl carboxamidoadenosine (CGS21680, A2A‐selective agonist), 9.3±0.1 for 5′‐N‐ethylcarboxamidoadenosine (NECA, A1/A2 agonist), 8.4±0.1 for 2‐chloroadenosine (A1/A2 agonist), 7.7±0.1 for N6‐(R)‐(phenylisopropyl)adenosine (R‐PIA, A1/A2B selective), and 6.8±0.2 for adenosine. The potency order (CGS21680=NECA>2‐chloroadenosine>R‐PIA>adenosine) supports A2A adenosine receptor‐mediated dilation in mouse coronary vessels. 0.2–2 μM of the A2B‐selective antagonist alloxazine failed to alter CGS21680 or 2‐chloroadenosine responses. pEC50s in rat were 6.7±0.2 for CGS21680, 7.3±0.1 for NECA, 7.6±0.1 for 2‐chloroadenosine, 7.2±0.1 for R‐PIA, and 6.2±0.1 for adenosine (2‐chloroadenosine>NECA=R‐PIA>CGS21680> adenosine), supporting an A2B adenosine receptor response. NO‐synthase antagonism with 50 μM NG‐nitro L‐arginine (L‐NOARG) increased resistance by ∼25%, and inhibited responses to CGS21680 (pEC50=9.0±0.1), 2‐chloroadenosine (pEC50=7.3±0.2) and endothelial‐dependent ADP, but not sodium nitroprusside (SNP). KATP channel blockade with 5 μM glibenclamide increased resistance by ∼80% and inhibited responses to CGS21680 in control (pEC50=8.3±0.1) and L‐NOARG‐treated hearts (pEC50=7.3±0.1), and to 2‐chloroadenosine in control (pEC50=6.7±0.1) and L‐NOARG‐treated hearts (pEC50=5.9±0.2). In summary, mouse coronary vessels are more sensitive to adenosine than rat vessels. A2A adenosine receptors mediate dilation in mouse coronary vessels vs A2B receptors in rat. Responses in the mouse involve a sensitive NO‐dependent response and KATP‐dependent dilation. British Journal of Pharmacology (2001) 133, 1063–1072; doi:10.1038/sj.bjp.0704170