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.

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.

(+-)-N6-endonorbornan-2-yl-9-methyladenine (N-0861) and its enantiomers: selective antagonists of A1-adenosine receptors in guinea pig isolated atria.

Adenosine and its metabolically stable analog 5'-N-ethylcarbox-amidoadenosine (NECA) induce negative inotropic, chronotropic and dromotrpic actions in the heart through activation of A1-adenosine receptors and relaxation of vascular smooth muscle through activation of A2-adenosine receptors. In vitro studies were carried out in order to determine the potency of the antagonist (+-)-N6-endonorbornan-2-yl-9-methyladenine (N-0861) and its two component enantiomers, WRC-0006(+) and WRC-0007(-), at the A1 receptors in the guinea pig atria and the A2 receptors in the guinea pig aorta. N-0861 competitively antagonized the negative inotropic responses induced by NECA in the eletrically paced left atrium (pKB = 6.24) and the negative chronotropic responses induced by NECA in the spontaneously beating right atrium (pKB = 6.29). WRC-0007 was 4-fold more potent (pKB = 6.51) than WRC-0006 (pKB = 5.86) at antagonizing the A1-adenosine receptors in the guinea pig left atrium. N-0861, WRC-0007 and WRC-0006 at high concentrations (> 3 x 10(-5) M) produced direct relaxations of the guinea pig aorta that masked to a small extent the A2 receptor antagonism by these compounds. The affinities of the antagonists for the A2 receptor in the aorta were calculated using the method of pharmacological resultant analysis. N-0861 was 47-fold less potent at the A2 receptor (pKB = 4.57) than it was at the A1 receptor. WRC-0006 was 2-fold more potent (pKB = 4.81) than WRC-0007 (pKB = 4.52) at the A2-adenosine receptor.(ABSTRACT TRUNCATED AT 250 WORDS)