Background. The bradykinin (BK)-induced endothelium-dependent relaxation is impaired in the presence of elevated potassium concentration enhancing the vasospastic tendency of large coronary arteries. Inhibition of the angiotensin-converting enzyme responsible for bradykinin degradation was found to enhance the endothelium-dependent relaxation by BK. The aim of the present study was to investigate the effect of phosphoramidon, known to inhibit a BK-metabolizing neutral endopeptidase enzyme, on relaxation of porcine-isolated coronary artery in depolarizing solution. Methods. Endothelium intact porcine coronary artery rings were studied in organ chambers. The rings were isometrically contracted with potassium chloride (30 mmol/L) and the response to BK (1 to 1,000 nmol/L)-induced relaxation was investigated in the presence of nitric oxide synthase inhibitor N(ω)-nitro-L-arginine (300 μmol/L) alone and in combination with the cyclooxygenase inhibitor indomethacin (10 μmol/L), and that of the inhibitor of calcium-dependent potassium channels tetraethylammonium (7 mmol/L). Under these conditions, phosphoramidon (10 μmol/L), an inhibitor of a neutral endopeptidase enzyme (EC.126.96.36.199.), which is responsible for the degradation of BK, was used to enhance the endothelium-dependent relaxation. Results. Phosphoramidon potentiated the maximum vasorelaxant effect of BK in N(ω)-nitro-L-arginine (control 26.6% ± 10.86% versus phosphoramidon 49.05% ± 4.52%; n = 6, p < 0.05) or in N(ω)-nitro-L-arginine + indomethacin-pretreated rings (control 20.7% ± 9.92% versus phosphoramidon 42.0% ± 12.26%; n = 5, p < 0.05) and this increased vasodilation was not modified by tetraethylammonium. Conclusions. In the present study phosphoramidon potentiated the effect of BK in the absence of nitric oxide and prostaglandins in porcine-isolated coronary artery. This effect did not depend on tetraethylammonium-sensitive potassium channels. Phosphoramidon may be a useful pharmacologic tool for preserving the vasorelaxing capacity of coronary arteries after cardioplegia. (C) 2000 by The Society of Thoracic Surgeons.
ASJC Scopus subject areas
- Pulmonary and Respiratory Medicine
- Cardiology and Cardiovascular Medicine