Oxygen-mediated pulmonary vasodilation and plasma levels of endothelin-1, atrial natriuretic peptide and cyclic GMP in patients with left-to-right shunt and pulmonary hypertension

This study was performed to evaluate the role of endogenous endothelin-l (ET-1), atrial natriuretic peptide (ANP) and cyclic guanosine monophosphate (cGMP) in patients with left-to-right shunt and pulmonary hypertension. Further objectives were to study a possible feedback mechanism between ANP and ET-1 and to examine the influence of ANP on cGMP plasma levels. Finally, the role of these hormones in oxygen-mediated pulmonary vasodilation was examined. Plasma concentrations of ET-I, ANP and cGMP were studied in 39 patients with congenital heart disease and left-to-right shunt. Blood samples were taken from the pulmonary artery and pulmonary vein sat cardiac catheterization at baseline and after breathing oxygen for 20 min. Patients were grouped according to the presence or absence of pulmonary hypertension (defined as mean Pp/Ps greater than or equal to 0.5). Patients with pulmonary hypertension (n = 18) were found to have significantly higher plasma ANP (665 [59-1358] versus 267 [47-832] pg/ml) and cGMP (21.5 [3.6-82.2] versus 7.8 [0-14.6] nM/L) levels than patients without pulmonary hypertension (n = 21). Pulmonary venous ET-I plasma concentrations were above normal limits in one patient only. ANP plasma levels were not related to ET-I and cGMP concentrations. There was no transpulmonary gradient for any of the factors. Pulmonary vasodilation in response to oxygen was found in 7 of 18 patients with PH, but was not associated with significant changes in ET-1, ANP or cGMP plasma concentrations. Patients with congenital heart disease and PH show an increase both in vasoconstrictive and vasodilating factors. The mechanism of oxygen-mediated vasodilation in these patients remains to be elucidated.