Pulmonary Vascular Smooth Muscle Contraction

Abstract

The purpose of this study was to determine the response of pulmonary vascular smooth muscle to (1) cellular depolarization (response to KCl), (2) α1-adrenergic receptor stimulation (response to phenylephrine, epinephrine, and norepinephrine), and (3) eicosinoid receptor stimulation (response to prostaglandin F2α, serotonin, and U46619). Isolated rat pulmonary artery rings were suspended on a fine wire tensiometer in individual organ chambers. After confirming endothelial integrity (response to acetylcholine), dose–response curves were constructed for each vasoactive agonist. The maximal developed tension as well as the dose required to produce 50% of maximal contraction (EC50) was determined for each agonist. The U46619, a stable thromboxane A2mimetic, and prostaglandin F2α(PGF2α) produced the greatest maximal developed tension in pulmonary vascular smooth muscle. This maximal contraction to U46619 and PGF2αwas the same as the maximal tension in response to cellular depolarization (KCl). The maximal tension developed to KCl and U46619 was significantly greater than to α1-adrenergic receptor stimulation and serotonin, 5HT. The maximal tension developed to PGF2αwas greater than the developed tension to 5HT. The dose response curves of α1-adrenergic receptor stimulation and U46619 were shifted to the left compared to PGF2αand 5HT. This study demonstrates that U46619 and PGF2αproduce the greatest maximal developed tension in pulmonary vascular smooth muscle. Furthermore, U46619 has the same potency as α1-adrenergic receptor stimulation, which is significantly greater than 5HT and PGF2α. These data may be helpful in the delineation of the pathophysiology of pulmonary hypertension due to adult respiratory distress syndrome.