Pulmonary hypertension in acute lung injury is due to impaired vasodilation with intact vascular contractility.

The major hemodynamic feature of acute lung injury (ALI) is pulmonary hypertension. Both endothelial-dependent and -independent pulmonary vasorelaxation is impaired in ALI due to endotoxemia. We hypothesized that endotoxemia selectively impairs relaxation of the pulmonary artery but does not impair contractility of pulmonary vascular smooth muscle (VSM). Our purpose was to determine the effect of endotoxemia (ETX) on the contractile response of pulmonary VSM to (1) tubular depolarization (KCl), (2) alpha 1-adrenoreceptor stimulation (phenylephrine, PE), (3) 5HT2 receptor stimulation (serotonin, 5HT), and (4) prostaglandin F2 alpha receptor stimulation. Pulmonary artery rings were isolated from rats 6 hr after injection of ETX, 20 mg/kg ip (n > or = 6), or saline (n > or = 6) and suspended on tensiometers in individual organ baths. Endothelial-dependent cGMP-mediated relaxation was determined using the receptor agonist acetylcholine (ACh) in rings preconstricted with PE. Dose-response curves were generated to each contractile agonist. Statistical comparison was performed using one-way ANOVA with post hoc Bonferonni-Dunn, P < 0.05 accepted as significant. Relaxation to ACh was 96.4 +/- 1.3% in controls vs 21.4 +/- 3.1% (P < 0.05) in endotoxin-treated rats. Endotoxin did not affect the maximal tension in response to the contractile agonists nor did it change the concentration required to produce 50% contraction (EC50). From these data we conclude that endotoxemia causes a decrease in vasorelaxation to the endothelial-dependent receptor agonist acetylcholine but does not impair agonist-induced contractility of pulmonary VSM. This suggests that pulmonary hypertension in ALI is mediated by impairment of pulmonary vasodilation with preservation of VSM contractility.