Adenosine A(2a) receptors increase arterial endothelial cell nitric oxide

Background. Adenosine(1) is a potent vasodilator of vascular smooth muscle. Endothelium-derived nitric oxide (NO) elicits vasodilation. We have previo usly reported that adenosine stimulates the production of NO from porcine c arotid arterial endothelial cells (PCAEC) via a receptor-mediated mechanism . This study was to determine whether adenosine also enhances NO production from human arterial endothelium and to define the involvement of adenosine A(1) and A(2) receptors. Materials and methods. Human iliac arterial endothelial cells (HIAEC) and P CAEC were harvested and cultured in dishes. NO production was evaluated wit h a NO electrode sensor which measured continuously real-time NO production . Results. NO content of the medium bathing HIAEC and PCAEC was significantly increased with adenosine (100 mu mol/L). Ethylcarboxamidoadenosine (NECA), a nonselective adenosine receptor agonist, and carboxyethyl-phenethylamino -ethylcarboxamidoadenosine (CGS-21680), a selective adenosine A(2a) recepto r agonist, increased NO production by HIAEC and PCAEC with respective EC50 values of 3.32 and 6.96 nmol/L for NECA and 30.97 and 29.47 nmol/L for CGS- 21680. Chlorofuryl-triazolo-quinazolinamine (CGS-15943; 1 mu mol/L), an ade nosine A(1) and A(2) receptor antagonist, and aminofuryltriazolotriazinyl-a minoethylphenol (ZM-241385; 1 mu mol/L), a selective adenosine A(2a) recept or antagonist, inhibited the effect of CGS-21680, Chlorocyclopentyl-adenosi ne (CCPA; 1 mu mol/L), an adenosine A(1) receptor agonist, significantly de pressed NO production by both HIAEC and PCAEC. This effect was inhibited by cyclopentyl-dipropylxanthine (DPCPX), a selective adenosine A(1) receptor antagonist. Conclusions. The results demonstrate that adenosine A(2a) receptors increas e, and adenosine A(1) receptors decrease, the production of NO by human and porcine arterial endothelial cells. (C) 1998 Academic Press.