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 effective pulmonary vasodilators in vitro (isolated arteries and perfused lungs) and in vivo in a variety of animal species. They prevent or reverse pulmonary vasoconstriction/contraction induced by a range of vasoconstrictor spasmogens or by alveolar hypoxia. 2. The pulmonary vasorelaxant effects of the KCO drugs are blocked by glibenclamide, do not depend on the endothelium, are dependent on the vasoconstrictor spasmogen used to contract the preparations and are enhanced in preparations taken from pulmonary hypertensive rats. 3. Selectivity for pulmonary compared with systemic vessels is seen in vessels from pulmonary hypertensive rats but not in the absence of pulmonary hypertension. 4. The pulmonary vasodilatation that is induced by (a) endothelium derived hyperpolarising factor, (b) endothelin, (c) increased pulmonary blood flow or (d) prolonged, severe hypoxia is probably due to potassium efflux through the same population of potassium channels as those on which the KCOs act. 5. Acute hypoxic pulmonary vasoconstriction, and also the depolarisation seen in arteries from chronically hypoxic rats, each involve inhibition of potassium efflux through glibenclamide-insensitive potassium channels. 6. It is suggested that the KCOs warrant investigation as possible therapeutic agents in the treatment of pulmonary hypertension.
Wanstall
J C
JC
Department of Physiology and Pharmacology, University of Queensland, Brisbane, Australia.
D000818:Animals; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy / Q000503:physiopathology; D066298:In Vitro Techniques; D015221:Potassium Channels / Q000187:drug effects*; D011652:Pulmonary Circulation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology* / Q000627:therapeutic use
D015221:Potassium Channels; D014665:Vasodilator Agents