VASORELAXATION OF NORADRENALINE-CONSTRICTED GUINEA-PIG AND RABBIT AORTA BY THE ADENOSINE ANALOG NECA - ROLES OF INTRACELLULAR AND EXTRACELLULAR CALCIUM

The action of the adenosine agonist, 5'-(N-ethylcarboxamido)-adenosine (NECA), at extracellular A(2), receptors of guinea-pig and rabbit aor tic rings was investigated. A near-maximum relaxant concentration (10( -5) M) of NECA was determined from cumulative concentration-response c urves 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+ mob ilization and influx of extracellular Ca2+ were examined using normal Ca2+ and Ca2+-free media. In normal Ca2+ medium, where both sources of Ca2+ are involved in the contraction to noradrenaline, NECA inhibited the contractions. In Ca2+-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 angiot ensin II (10(-6) M) in both normal and Ca2+-free media, which are medi ated via release of intracellular Ca2+, were also not inhibited by NEC A. These results indicate that the activation of extracellular A(2) ad enosine 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 exa mined in guinea-pig aortae in Ca2+-free medium and after exposure to a ngiotensin to deplete intracellular Ca2+ stores. Contractions were the n 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 nor mal Ca2+ medium, suggests that NECA causes vasorelaxation in the aorta by interfering with the Ca2+ influx via receptor-operated channels in duced by noradrenaline.