title: The endothelium of the rat renal artery plays an obligatory role in A2 adenosine receptor-mediated relaxation induced by 5'-N-ethylcarboxamidoadenosine and N6-cyclopentyladenosine.
abstract: Studies were undertaken in the rat isolated renal artery in order to determine if adenosine receptor agonists were capable of inducing the release of nitric oxide from the renovascular endothelium. N6-cyclopentyladenosine (CPA) and 5'-N-ethylcarboxamidoadenosine (NECA) produced concentration-dependent relaxations in endothelium intact renal artery rings. The NECA curve was biphasic with a first phase pA50 of 6.05. The CPA curve was monophasic with a pA50 of 4.35. In the absence of endothelium the curves to both NECA and CPA were monophasic with pA50 values of 3.37 and 3.50, respectively. The A2a adenosine receptor-selective agonist CGS21680 (2-[p-(2-carboxyethyl)-phenethylamino]-5'-N-ethylcarboxamidoadenos ine) was inactive in endothelium intact tissues. Relaxant responses to CPA and NECA in the presence of endothelium were antagonized by 8-p-sulfophenyltheophylline and by 1,3-dipropyl-8-cyclopentylxanthine only at a nonselective concentration (3 x 10(-6) M) suggesting activation of A2 adenosine receptors. The responses to CPA and NECA in the absence of endothelium are not due to activation of A1 or A2 adenosine receptor subtypes because they are resistant to blockade by these xanthines. CPA and NECA responses in the presence of endothelium were inhibited by NG-nitro-L-arginine methylester (L-NAME), a nitric oxide synthase inhibitor, but not by the cyclooxygenase inhibitor indomethacin or the K+ATP channel antagonist glibenclamide. These results suggest that the rat renal artery contains A2b adenosine receptors that are located exclusively on the endothelium and cause the release of nitric oxide.
authors.affiliation: Department of Pharmacology, Whitby Research, Inc., Richmond, Virginia.
authors.forename: P L
authors.initials: PL
authors.lastname: Martin
authors.forename: A A
authors.initials: AA
authors.lastname: Potts
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D019830:Adenosine-5'-(N-ethylcarboxamide); D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D005905:Glyburide / Q000494:pharmacology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology; D058906:Purinergic P1 Receptor Agonists; D051381:Rats; D017207:Rats, Sprague-Dawley; D018047:Receptors, Purinergic P1 / Q000187:drug effects* / Q000502:physiology; D012077:Renal Artery / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D012079:Renal Circulation; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology*; D014970:Xanthines / Q000494:pharmacology
chemical_list: D058906:Purinergic P1 Receptor Agonists; D018047:Receptors, Purinergic P1; D014665:Vasodilator Agents; D014970:Xanthines; D009599:Nitroprusside; D009569:Nitric Oxide; D019830:Adenosine-5'-(N-ethylcarboxamide); C048599:N(6)-cyclopentyladenosine; C031433:8-(4-sulfophenyl)theophylline; D001120:Arginine; C051360:1,3-dipropyl-8-cyclopentylxanthine; D013806:Theophylline; D000241:Adenosine; D007545:Isoproterenol; D005905:Glyburide; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin