Pulmonary Hemodynamic Responses to Brain Natriuretic Peptide and Sildenafil in Patients With Pulmonary Arterial Hypertension* James R. Klinger, MD; Sejal Thaker, MD; Jeanne Houtchens, RN; Ioana R. Preston, MD; Nicholas S. Hill, MD; and Harrison W. Farber, MD Study objectives: Brain natriuretic peptide (BNP) blunts hypoxic pulmonary hypertension in animal models, but its acute hemodynamic effects in patients with pulmonary arterial hyperten- sion (PAH) are not known. The aim of this study was to determine if human B-type natriuretic peptide is a safe and efficacious pulmonary vasodilator in patients with PAH and if the pulmonary hemodynamic effects are potentiated by phosphodiesterase inhibition. Design: Open-label study. Setting: Medical ICUs of three tertiary care hospitals in New England. Patients: Thirteen consecutive adult patients undergoing right-heart catheterization and a pulmonary vasodilator trial for the initial evaluation of PAH. Interventions: Patients were administered inhaled nitric oxide (iNO), IV epoprostenol, and a 3-h infusion of BNP alone and 1 h after an oral dose of the phosphodiesterase-5 inhibitor sildenafil. Results: iNO and sildenafil alone decreased mean pulmonary artery pressure (mPAP) without a significant fall in pulmonary vascular resistance (PVR). Epoprostenol decreased both mPAP and PVR. BNP alone had no significant effect on pulmonary hemodynamics, but the combination of sildenafil plus BNP decreased mPAP and PVR for up to 6 h after stopping BNP. The decrease in mPAP with sildenafil plus BNP ( SE) was greater than after 1 h of sildenafil alone (44.6  3.8 to 40.6  3.9 mm Hg, p  0.027). An acute vasodilator response, defined as a decrease in mPAP > 10 mm Hg and end mPAP < 40 mm Hg, was seen in 0 of 8 patients with iNO, 1 of 13 patients with epoprostenol, 0 of 13 patients with BNP, and 4 of 12 patients with sildenafil plus BNP. BNP decreased mean systemic arterial pressure (5.6  2.8 mm Hg) but had no effect on cardiac output or systemic vascular resistance. Conclusions: A 3-h BNP infusion does not significantly improve pulmonary hemodynamics in most patients with PAH but is well tolerated and augments the acute pulmonary vasodilator effect of sildenafil. (CHEST 2006; 129:417– 425) Key words: cyclic guanosine monophosphate; hypertension, pulmonary; natriuretic peptides; nitric oxide; sildenafil; phosphodiesterase inhibitors; prostaglandin Abbreviations: ANP = atrial natriuretic peptide; BNP = brain natriuretic peptide; cGMP = cyclic guanosine mono- phosphate; iNO = inhaled nitric oxide; mPAP = mean pulmonary arterial pressure; NPR-A = natriuretic peptide receptor-A; PAH = pulmonary arterial hypertension; PAP = pulmonary arterial pressure; PCWP = pulmonary capillary wedge pressure; PDE-5 = phosphodiesterase-5; PVR = pulmonary vascular resistance; WHO = World Health Orga- nization O riginally discovered in the porcine brain, brain natriuretic peptide (BNP) is a member of the natriuretic peptide family of proteins that share a similar 17 amino acid ring structure necessary for its biological activity. 1 Like atrial natriuretic peptide (ANP), BNP is highly expressed in the heart. 2 Both peptides activate the particulate guanylyl cyclase- linked receptor, natriuretic peptide receptor-A (NPR-A) to raise intracellular cyclic guanosine monophosphate (cGMP) levels that mediate their potent diuretic and vasorelaxant effects. 3 In addition to their hemodynamic effects, natriuretic peptides Original Research VASCULAR DISEASES www.chestjournal.org CHEST / 129 / 2 / FEBRUARY, 2006 417