THE PULMONARY VASODILATOR PROPERTIES OF POTASSIUM CHANNEL OPENING DRUGS

1. This article reviews the effects of potassium channel opening drugs (KCOs) on blood vessels of the pulmonary circulation. KCOs are effect ive pulmonary vasodilators in vitro (isolated arteries and perfused lu ngs) and in vivo in a variety of animal species. They prevent or rever se pulmonary vasoconstriction/contraction induced by a range of vasoco nstrictor spasmogens or by alveolar hypoxia. 2. The pulmonary vasorela xant effects of the KCO drugs are blocked by glibenclamide, do not dep end on the endothelium, are dependent on the vasoconstrictor spasmogen used to contract the preparations and are enhanced in preparations ta ken from pulmonary hypertensive rats. 3. Selectivity for pulmonary com pared with systemic vessels is seen in vessels from pulmonary hyperten sive rats but not in the absence of pulmonary hypertension. 4. The pul monary vasodilatation that is induced by (a) endothelium derived hyper polarising factor, (b) endothelin, (c) increased pulmonary blood flow or (d) prolonged, severe hypoxia is probably due to potassium efflux t hrough the same population of potassium channels as those on which the KCOs act. 5. Acute hypoxic pulmonary vasoconstriction, and also the d epolarisation seen in arteries from chronically hypoxic rats, each inv olve inhibition of potassium efflux through glibenclamide insensitive potassium channels. 6. It is suggested that the KCOs warrant investiga tion as possible therapeutic agents in the treatment of pulmonary hype rtension.