Abstract:The present experiments were undertaken in order to examine the effect of adenosine in isolated rat aorta, to investigate the possible role of intact endothelium and endothelial relaxing factors in this action and to determine which population of adenosine receptors is involved in rat aorta response to adenosine. Adenosine (0.1-300 mM) produced concentration-dependent (intact rings: pD 2 Ω4.39∫0.09) and endothelium-independent (denuded rings: pD 2 Ω4.52∫0.12) relaxation of isolated rat aorta. In the presence of high concentration of K π (100 mM) adenosine-evoked relaxation was significantly reduced (maximal relaxation in denuded rings: control -92.1∫9.8 versus K π -54.4∫5.0). Similar results were obtained after incubation of ouabain (100 mM) or glibenclamide (1 mM). In K π -free solution, K π (1-10 mM)-induced rat aorta relaxant response was significantly inhibited by ouabain (100 mM). Application of indomethacin (10 mM), N G -nitro-L-arginine (10 mM) or tetraethylammonium (500 mM) did not alter the adenosine-elicited effect in rat aorta. 8-(3-Chlorostyril)-caffeine (0.3-3 mM), a selective A 2A -receptor antagonist, significantly reduced adenosine-induced relaxation of rat aorta in a concentration-dependent manner (pK B Ω6.57). Conversely, 1,3-dipropyl-8-cyclopentylxanthine (10 nM), an A 1 -receptor antagonist, did not affect adenosine-evoked dilatation. These results indicate that in isolated rat aorta, adenosine produces endothelium-independent relaxation, which is most probably dependent upon activation of smooth muscle Na π /K π -ATPase, and opening of ATP-sensitive K π channels, to a smaller extent. According to receptor analysis, vasorelaxant action of adenosine in rat aorta is partly induced by activation of smooth muscle adenosine A 2A receptors.
It has been previously shown that vasoactive intestinal polypeptide (VIP) induces endothelium-dependent relaxation of the human uterine artery. However, the nature of the mediator of the VIP-induced endothelium-dependent relaxation of the human uterine artery has not yet been determined. Therefore these experiments were undertaken to examine the effects of VIP on human uterine arteries and to establish the role of various endothelial factors on the relaxation induced by VIP. The experiments were performed on isolated human uterine arterial rings. VIP (0.3-100 nM) induced a concentration-dependent relaxation of human uterine arteries with intact endothelium (pEC50 = 8.06+/-0.14, n = 28). After the removal of the endothelium this relaxation was abolished (n = 6). Indomethacin (10 microM), a cyclooxygenase inhibitor, and diethylcarbamazine (100 microM), a lipoxygenase blocker, had no effects on VIP-induced relaxation. In contrast, methylene blue (10 microM), a blocker of guanylate cyclase, NG-monomethyl-L-arginine (10 microM), an inhibitor of nitric oxide (NO) synthase, and 4-aminopyridine (1 mM), a non-selective blocker of K+ channels, antagonized the effect of VIP with suppression of maximal VIP-induced relaxation. Non-competitive antagonism with methylene blue revealed that the pKa value for VIP-receptor complex was 8.10+/-0.10 (n = 6) and the receptor reserve expressed as KA/EC50 was 0.89+/-0.11, where pKa = log10KA, and KA is the dissociation constant of VIP-receptor complex. Therefore, on the basis of the results presented, we can conclude that VIP induces endothelium-dependent relaxation in human uterine arteries, acting as a partial agonist on this blood vessel. It appears that endothelium-dependent relaxation induced by VIP in human uterine artery can be entirely explained by the release of NO from endothelial cells.
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