Role of nitric oxide in adenosine receptor-mediated relaxation of porcine coronary artery

Abstract

In the present study, using porcine coronary artery rings in vitro, we examined the role of the nitric oxide (NO) pathway in endothelium-dependent vasorelaxant effects of the 5'-uronamide adenosine agonists, 5'-(N-ethylcarboxamido)adenosine (NECA) and 2-[p-(2-carboxyethyl)]phenylethyl-amino-5'-N-ethylcarboxamidoadenosine (CGS-21680) as opposed to the endothelium-independent actions of the C2- and N6-substituted analogues, 2-chloroadenosine (CAD) and N6-cyclopentyladenosine (CPA). The NO synthase inhibitor, NG-monomethyl-L-arginine (L-NMMA, 30 microM), and the NO-destroying agent, 6-anilino-5,8-quinolinedione (LY-83583, 10 microM), attenuated the relaxations of endothelium-intact but not -denuded rings to NECA and CGS-21680. The effect of L-NMMA on NECA-induced relaxation was reversed by L-arginine (100 microM), a substrate for NO synthesis. In the endothelium-intact tissues, both NECA and CGS-21680 elicited enhanced production of nitrite, a stable metabolite of NO. This was also attenuated by L-NMMA or endothelium removal. Furthermore, NECA (10 microM) induced augmentation of guanosine 3',5'-cyclic monophosphate (cGMP) production in the intact arteries, which was also inhibited by L-NMMA, LY-83583, or endothelium removal. In contrast, vasorelaxant responses generated by CAD and CPA were not altered by either L-NMMA or LY-83583. Both agents (10 microM) were also unable to alter nitrite and/or guanosine 3',5'-cyclic monophosphate (cGMP) levels of the coronary artery.(ABSTRACT TRUNCATED AT 250 WORDS)

Vasoconstrictor and Vasodilator Effects of Adenosine in the Mouse Kidney due to Preferential Activation of A1 or A2 Adenosine Receptors

“…The abolished vasodilatation in the superficial vascular bed by ZM-241385 indicates that NO formation is primarily the result of A2aAR activation. These conclusions agree with previous studies in excised renal and nonrenal vessel preparations showing consistent increases in NOS activity and NO release in response to adenosine, usually through an A2AR-mediated process (Zanzinger and Bassenge, 1993 ; Martin TABLE 5 Effect of intravenous infusion of adenosine at 5, 10, and 20 g/min after injection of the nonspecific NOS inhibitor L-NAME on MAP, SBF, and SVR in wild-type (A1ARϩ/ϩ), A1 adenosine receptor knockout mice (A1ARϪ/Ϫ), and mice deficient in endothelial NOS (eNOSϪ/Ϫ) and Potts, 1994; Abebe et al, 1995;Grbovic et al, 2000). Adenosine has also been shown to dilate rabbit renal arteries through an undefined endothelial relaxing factor that does not seem to be NO (Rump et al, 1999).…”

A2B adenosine receptors mediate relaxation of the pig intravesical ureter: adenosine modulation of non adrenergic non cholinergic excitatory neurotransmission

“…Thus, part of the relaxing e ect produced by adenosine in the rabbit isolated heart is mediated through release of prostaglandins (Ciabattoni & Wennmalm, 1985;Karwatowska-Prokopczuk et al, 1988). Adenosine, on the other hand, promotes the release of NO from vascular endothelium (Vials & Burnstock, 1993;Abebe et al, 1995;Li et al, 1995;Danialou et al, 1997) and smooth muscle (Ikeda et al, 1997). However, in the pig intravesical ureter, indomethacin and L-NOARG, which inhibit prostanoid production and NO-synthase activity, respectively, did not modify the relaxations to adenosine, suggesting that adenosine relaxes the ureteral smooth muscle via a prostaglandins-and NO-independent mechanism.…”

Up-regulation of A2B adenosine receptor in A2A adenosine receptor knockout mouse coronary artery

“…However, there are very few functional studies demonstrating whether NO release is responsible for A 2A AR mediated coronary vasodilation. Previously, a study from our group found that N Gmethyl-L-arginine (L-NMA, 30 µM), a NO synthase inhibitor, attenuated the relaxations of endothelium-intact but not -denuded rings to adenosine-5′N-ethylcarboxamide (NECA) and CGS-21680 in porcine coronary arterial rings [5]. Beyond these reports in isolated tissues, there is no other evidence of how significant a role NO plays in A 2A AR mediated coronary vasodilation.…”