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.
Stewart
A G
AG
Department of Medicine and Pharmacology, University of Sheffield, UK.
Sheedy
W
W
Thompson
J S
JS
Morice
A H
AH
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism; D004148:Dioxolanes / Q000494:pharmacology*; D004151:Dipeptides / Q000494:pharmacology*; D000860:Hypoxia / Q000378:metabolism*; D007279:Injections, Subcutaneous; D008297:Male; D015260:Neprilysin / Q000037:antagonists & inhibitors*; D011651:Pulmonary Artery / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D000700:Analgesics; D004148:Dioxolanes; D004151:Dipeptides; C056319:Sch 34826; D009320:Atrial Natriuretic Factor; D015260:Neprilysin