Comparison of relaxation responses to multiple vasodilators in TxA2‐analog and endothelin‐1‐precontracted pulmonary arteries

Abstract

Peri-operative pulmonary hypertension can lead to right ventricular dysfunction and to an increase in morbidity and mortality. Altered function of the pulmonary vascular endothelium and vasoconstriction play a crucial role in the development of elevated pulmonary vascular resistance. Because pulmonary artery vasoreactivity is dependent on many factors including the constricting agent that precipitated the event therefore the aim of the current study was to investigate the effectiveness of different classes of vasodilator agents to reverse endothelin-1 (ET-1) or thromboxane A(2) (TxA(2))-induced vasoconstriction in porcine pulmonary artery (PA) in vitro. Relaxation responses to vasodilatory drugs were studied in PA precontracted with ET-1 (1 x 10(-8) M) or TxA(2) analog (U46619, 1 x 10(-8) M). All vasodilating drugs were added in a cumulative fashion and isometric tension measurements were obtained using an organ chamber technique. In both groups relaxation responses to the vasodilators were dose dependent. When ET-1 was used as a constrictor nitroglycerin and milrinone caused nearly complete (80-100%) relaxation, whereas other agents were of limited effectiveness (40-50%). On the other hand, in the vessels constricted with U46619, olprinone, indomethacin, prostaglandin E(1) (PGE(1)), nitroglycerin, milrinone and clevidipine induced complete (90-110%) vasodilatation but brain natriuretic peptide (BNP), L-arginine, and isoproterenol relaxed the vessels maximally by 45-60%. Nitroglycerin and milrinone are very effective in reversing ET-1 and U46619-induced pulmonary vasoconstriction in vitro. The effectiveness of other drugs studied was dependent on the type of constrictor used. BNP, L-arginine and isoproterenol were shown to have minimal vasodilatory effects in porcine PA.