ICI-118,551 is a selective subtype β2 adrenergic receptor (adrenoreceptor) antagonist. ICI-118,551 binds to the β2 subtype with at least 100 times greater affinity than to other subtypes of the beta adrenoceptor β1 or β3. Pharmacological experiments proved that the right shift of the norepinephrine dose-response curve by ICI-118,551 was mediated via a beta(2)-adrenoceptor/G(i/o) protein-dependent pathway enhancing NO production in the endothelium. These results were corroborated in beta-adrenoceptor and endothelial NO synthase knockout mice where ICI had no effect. ICI-118,551 increased vascular lumen diameter in lung sections and reduced pulmonary arterial pressure under normoxia and under hypoxia in the isolated perfused lung model. These effects were found to be physiologically relevant, because ICI-118,551 specifically decreased pulmonary but not systemic blood pressure in vivo. Thus, it has been suggested that ICI-118,551 is a pulmonary arterial-specific vasorelaxant and might be a potential novel therapeutic agent for the treatment of pulmonary arterial hypertension. It was also demonstrated that systemic topical administration of ICI 118,551 results in decreased intraocular pressure in both eyes of rabbits, indicating that at least part of the ocular hypotensive effect of topical ICI 118,551 is mediated through systemic absorption. However, ICI 118,551 did not lower blood pressure in hypertensive patients known to respond to therapy with atenolol or propranolol.