Effects of SCH 34826, a neutral endopeptidase inhibitor, on hypoxic pulmonary vascular remodelling.

Atrial natriuretic peptide (ANP) is a potent vasodilator of hypoxia constricted pulmonary vessels. Chronic infusions of ANP have been shown to limit the anatomical pulmonary vascular remodelling associated with chronic exposure to a 10% oxygen environment. SCH 34826 elevates plasma ANP by inhibition of the enzyme neutral endopeptidase EC 3.4.24.11. We administered by subcutaneous injection 90 mg/kg SCH 34826 twice daily into six male Wistar rats. Six littermate controls received 1 ml of 0.4% aqueous methyl cellulose vehicle. All animals were exposed to a 10% oxygen environment for 2 weeks. Administration of SCH 34826 caused a significant reduction in the hypoxia-induced pulmonary vascular remodelling and right ventricle hypertrophy. Neutral endopeptidase inhibition by drugs such as SCH 34826 could prove useful in conditions characterized by pulmonary hypertension and pulmonary vascular remodelling.