Pulmonary vascular smooth muscle contraction.

The purpose of this study was to determine the response of pulmonary vascular smooth muscle to (1) cellular depolarization (response to KC1), (2) alpha 1-adrenergic receptor stimulation (response to phenylephrine, epinephrine, and norepinephrine), and (3) eicosinoid receptor stimulation (response to prostaglandin F 2 alpha, 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 A2 mimetic, and prostaglandin F 2 alpha, (PGF 2 alpha) produced the greatest maximal developed tension in pulmonary vascular smooth muscle. This maximal contraction to U46619 and PGF 2 alpha, was the same as the maximal tension in response to cellular depolarization (KCI). The maximal tension developed to KCI and U46619 was significantly greater than to alpha 1-adrenergic receptor stimulation and serotonin, 5HT. The maximal tension developed to PGF 2 alpha was greater than the developed tension to 5HT. The dose response curves of alpha 1-adrenergic receptor stimulation and U46619 were shifted to the left compared to PGF 2 alpha and 5HT. This study demonstrates that U46619, and PGF 2 alpha produce the greatest maximal developed tension in pulmonary vascular smooth muscle. Furthermore, U46619 has the same potency as alpha 1-adrenergic receptor stimulation, which is significantly greater than 5HT and PGF 2 alpha. These data may be helpful in the delineation of the pathophysiology of pulmonary hypertension due to adult respiratory distress syndrome.