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

Low frequency (2Hz) nerve-stimulation induced [H-3]noradrenaline ([H-3]NA) release has been measured from the isolated main pulmonary artery of the rabbit in the presence of uptake blockers (cocaine, 3 x 10(-5)M; corticosterone, 5 x 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 [H-3]NA which failed to show close concentration-dependency. Large concentration of pinacidil (10(-4)M) increased the ratio of [H-3]NA release from 0.99 +/- 0.02 to 1.29 +/- 0.05; P<0.0005). On the other hand, pinacidil inhibited the nerve-evoked contractions in a concentration-dependent manner. 10(-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' Ca2+-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. (C) 1997 Academic Press Limited.