Vasorelaxation of noradrenaline-constricted guinea-pig and rabbit aorta by the adenosine analogue NECA: roles of intra-and extracellular calcium.

The action of the adenosine agonist, 5'-(N-ethylcarboxamido)-adenosine (NECA), at extracellular A2 receptors of guinea-pig and rabbit aortic rings was investigated. A near-maximum relaxant concentration (10(-5) M) of NECA was determined from cumulative concentration-response curves in aortae precontracted with noradrenaline. The effects of this concentration of NECA upon the noradrenaline-induced contractions were measured as the ratio of the contractions obtained before and, in the same tissue, after addition of NECA. This ratio was compared with the control ratio obtained in paired tissues after adding vehicle between the first and second contraction. The roles of intracellular Ca2+ mobilization and influx of extracellular Ca2+ were examined using normal Ca2+ and Ca(2+)-free media. In normal Ca2+ medium, where both sources of Ca2+ are involved in the contraction to noradrenaline, NECA inhibited the contractions. In Ca(2+)-free conditions, the phasic contraction to noradrenaline was mediated via the intracellular Ca2+ pool and was not inhibited by NECA. The contractions of the guinea-pig aorta to angiotensin II (10(-6) M) in both normal and Ca(2+)-free media, which are mediated via release of intracellular Ca2+, were also not inhibited by NECA. These results indicate that the activation of extracellular A2 adenosine receptors by NECA does not cause vasorelaxation by interfering with the release of intracellular Ca2+ by noradrenaline. The effects of NECA on contractions, due to influx of extracellular Ca2+, were examined in guinea-pig aortae in Ca(2+)-free medium and after exposure to angiotensin to deplete intracellular Ca2+ stores. Contractions were then induced by restoring the Ca2+ to the medium. These contractions were not inhibited by NECA, but when noradrenaline was present during the restoration of Ca2+, NECA was inhibitory. This and the evidence in normal Ca2+ medium, suggests that NECA causes vasorelaxation in the aorta by interfering with the Ca2+ influx via receptor-operated channels induced by noradrenaline.