Pre-junctional stimulatory and post-junctional inhibitory effects of pinacidil in the isolated main pulmonary artery of the rabbit under different experimental conditions

Abstract Low frequency (2 Hz) nerve-stimulation induced [ 3 H]noradrenaline ([ 3 H]NA) release has been measured from the isolated main pulmonary artery of the rabbit in the presence of uptake blockers (cocaine, 3×10 −5 M; corticosterone, 5×10 −5 ), with parallel measurements of post-junctional contractile responses. The K + ATP -channel opener pinacidil (10 −6 –10 −4 M), slightly potentiated the nerve-evoked release of [ 3 H]NA which failed to show close concentration-dependency. Large concentration of pinacidil (10 −4 M) increased the ratio of [ 3 H]NA release from 0.99±0.02 to 1.29±0.05; P −4 M caused nearly 70% inhibition of contractile response. The pre- and post-junctional effects of pinacidil were studied under the following experimental conditions: (1) exogenously applied l-NA; (2) excess K + ; (3) «L-type» Ca 2+ -channel activation (BAY K 8644); (4) K + -channel inhibition (4-AP); and (5) Na + -pump inhibition/reactivation. Pinacidil (10 −4 M) retained its marginal NA-release stimulatory effect in all cases. However, pinacidil inhibited the contraction of smooth muscle, although to a different extent, in all of the experimental conditions used in our study.