PINACIDIL-INDUCED RELAXATION IN PULMONARY-ARTERIES ISOLATED FROM PULMONARY HYPERTENSIVE AND NORMOTENSIVE RATS AND PRE-CONTRACTED WITH DIFFERENT SPASMOGENS

Vasorelaxant responses to the potassium channel opening drug, pinacidi l, were obtained on preparations of pulmonary artery and aorta taken f rom rats with pulmonary hypertension (induced by chronic hypoxia or mo nocrotaline) and pre-contracted either submaximally with endothelin-1 (ET-1), PGF(2 alpha), U46619 (thromboxane-mimetic) or noradrenaline (N A), or with 80 mM K+. In pulmonary artery, but not aorta, from pulmona ry hypertensive rats the maximum relaxant response to pinacidil was in creased, when compared with data in control rats, irrespective of the spasmogen used to precontract the tissues. The increase in maximum was associated with relaxation to below the tissue resting baseline and p robably reflected the presence of inherent contractile tone in arterie s from pulmonary hypertensive rats. In addition the potency (-log EC(5 0) of pinacidil was increased in pulmonary arteries from pulmonary hyp ertensive rats hut this was seen only in preparations contracted with ET-1 (30-fold increase) or NA (seven-fold increase) and mot in those c ontracted with PGF(2 alpha), U46619 or K+. As a result, in ET-1-contra cted preparations from pulmonary hypertensive rats pinacidil was 29-fo ld more potent on pulmonary artery than on aorta. To explain the incre ase in potency it is speculated that during the development of pulmona ry hypertension the mechanism whereby ET-1, and NA contract pulmonary arteries may change from one in which Ca2+ influx plays only a minor r ole to one in which Ca2+ influx predominates, although no direct evide nce to support this speculation has yet been obtained.