Response of the pulmonary circulation to acetylcholine, calcitonin gene-related peptide, substance P and oral nicardipine in patients with primary pulmonary hypertension

Abstract

Endothelium-dependent vasodilation of the pulmonary vascular bed was investigated in five patients with primary pulmonary hypertension. Three endothelium-dependent vasodilators (acetylcholine, calcitonin gene-related peptide and substance P [in two patients]) were infused sequentially into the right atrium, followed by nicardipine given orally during full hemodynamic monitoring.Acetylcholine, calcitonin gene related peptide and substance P had no effect on pulmonary artery pressure, total pulmonary vascular resistance or cardiac output, although calcitonin gene-related peptide significantly decreased systemic arterial systolic pressure from 132 ± 34 to 113 ± 33 mm Hg. In contrast, oral nicardipine decreased total pulmonary vascular resistance from 23 ± 12 to 13 ± 8 U, with a concomitant increase in cardiac output from 3.1 ± 1 to 4.7 +- 2 liters · min−1and decrease in systemic vascular resistance from 30 ± 9 to 13 ± 4 U.Thus, despite the presence of a reversible component in these five patients with primary pulmonary hypertension, pulmonary vascular resistance did not decrease ia response to the infused endothelium-dependent vasodilator agents, indicating that endothelium-dependent vasodilation is impaired ia these patients.