Predominant role of A1 adenosine receptors in mediating adenosine induced vasodilatation of rat diaphragmatic arterioles: involvement of nitric oxide and the ATP‐dependent K+ channels

• Published in: British journal of pharmacology 1997-08, Vol.121 (7), p.1355-1363
• Main Authors: Danialou, Gawiyou, Vicaut, Eric, Sambe, Abdoulaye, Aubier, Michel, Boczkowski, Jorge
• Format: Article
• Language: English
• Subjects: Adenosine - pharmacology; adenosine receptors; Adenosine Triphosphate - pharmacology; Animals; arterioles; Arterioles - drug effects; Arterioles - physiology; Biological and medical sciences; Blood vessels and receptors; Diaphragm; Diaphragm - blood supply; DMPX; DPCPX; DPMA; DPSPX; Fundamental and applied biological sciences. Psychology; glibenclamide; Male; nitric oxide; Nitric Oxide - physiology; Potassium - physiology; Rats; Rats, Sprague-Dawley; Receptors, Purinergic P1 - physiology; R‐PIA; Vasodilation - drug effects; Vertebrates: cardiovascular system
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1038/sj.bjp.0701247

We investigated, by intravital microscopy in rats, the role of the subtypes of adenosine receptors A1 (A1/AR) and A2 (A2AR) in mediating adenosine‐induced vasodilatation of second and third order arterioles of the diaphragm. Adenosine, and the A1AR selective agonists R(−)‐N6‐(2‐phenylisopropyl)‐adenosine (R‐PIA) and N6‐cyclo‐pentyl‐adenosine (CPA) induced a similar concentration‐dependent dilatation of diaphragmatic arterioles. The non selective A2AR subtype agonist N6‐[2‐(3,5‐dimethoxyphenyl)‐2‐(2‐methylphenyl) ethyl]adenosine (DPMA) also dilated diaphragmatic arterioles but induced a significantly smaller dilatation than adenosine. By contrast the selective A2aAR subtype agonist 2‐[p‐(2‐carboxyethyl)phenyl amino]‐5′‐N‐ethyl carboxamido adenosine (CGS 21680) did not modify diaphragmatic arteriolar diameter. The non selective adenosine receptor antagonist 1,3‐dipropyl‐8‐p‐sulphophenylxanthine (SPX, 100 μM) and the selective A1AR antagonist 8‐cyclopentyl‐1,3‐dipropylxanthine (CPX, 50 nM) significantly attenuated adenosine‐induced dilatation of diaphragmatic arterioles. By contrast, adenosine significantly dilated diaphragmatic arterioles in the presence of A2AR antagonist 3,7‐dimethyl‐1‐propargylxanthine (DMPX, 10 μM). The dilatation induced by adenosine was unchanged by the mast cell stabilizing agent sodium cromoglycate (cromolyn, 10 μM). The nitric oxide (NO) synthase inhibitor Nω‐nitro‐L‐arginine (L‐NOARG, 300 μM) attenuated the dilatation induced by adenosine, and by the A1AR and A2AR agonists. The ATP‐dependent K+ channel blocker glibenclamide (3 μM) significantly attenuated diaphragmatic arteriolar dilatation induced by adenosine and by the A1AR agonists R‐PIA and CPA. By contrast, glibenclamide did not significantly modify arteriolar dilatation induced by the A2AR agonist DPMA. These findings suggest that adenosine‐induced dilatation of diaphragmatic arterioles in the rat is predominantly mediated by the A1AR, via the release of NO and activation of the ATP‐dependent K+ channels.