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 (E T-1), atrial natriuretic peptide (ANP) and cyclic guanosine monophosphate ( cGMP) in patients with left-to-right shunt and pulmonary hypertension. Furt her 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, th e role of these hormones in oxygen-mediated pulmonary vasodilation was exam ined. Plasma concentrations of ET-I, ANP and cGMP were studied in 39 patien ts with congenital heart disease and left-to-right shunt. Blood samples wer e taken from the pulmonary artery and pulmonary vein sat cardiac catheteriz ation at baseline and after breathing oxygen for 20 min. Patients were grou ped according to the presence or absence of pulmonary hypertension (defined as mean Pp/Ps greater than or equal to 0.5). Patients with pulmonary hyper tension (n = 18) were found to have significantly higher plasma ANP (665 [5 9-1358] 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). P ulmonary venous ET-I plasma concentrations were above normal limits in one patient only. ANP plasma levels were not related to ET-I and cGMP concentra tions. There was no transpulmonary gradient for any of the factors. Pulmona ry 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 plas ma concentrations. Patients with congenital heart disease and PH show an in crease both in vasoconstrictive and vasodilating factors. The mechanism of oxygen-mediated vasodilation in these patients remains to be elucidated.