Pulmonary versus systemic effects of vasodilator drugs: an in vitro study in isolated intrapulmonary and mesenteric arteries of neonatal piglets

Abstract

The ability of several vasodilators to inhibit the responses to noradrenaline and U46619 (a thromboxane A 2 analog) in isolated pulmonary and mesenteric arteries of neonatal piglets was compared. In pulmonary arteries, acetylcholine produced endothelium-dependent relaxations (pIC 50 = about 6.8) while, in mesenteric arteries, a relaxant (≤ 10 −7 M) or a contractile response (≥ 10 −6 M) was observed. Sodium nitroprusside produced relaxant effects in pulmonary and mesenteric arteries contracted by noradrenaline (pIC 50 = 6.6 and 6.0, respectively) and U46619 (pIC 50 = 5.4 and 6.7, respectively). ATP induced an endothelium-independent relaxation in pulmonary arteries (pIC 50 = about 4) but in mesenteric arteries it produced weak relaxant effects. In resting mesenteric arteries, ATP induced a concentration-dependent contraction which was not observed in pulmonary arteries. Prostaglandin E 1 induced a concentration-dependent relaxation in pulmonary arteries (pIC 50 = about 6). In mesenteric arteries, prostaglandin E 1 at < 10 −6 M produced a contractile effect whereas, at higher concentrations, a relaxant response was observed. The α-adrenoceptor antagonist tolazoline had no effect on arteries contracted by U46619 but relaxed arteries contracted by noradrenaline being slightly more potent in mesenteric than in pulmonary arteries (pIC 50 = 5.1 and 4.8, respectively). Nifedipine (> 10 −7 M) relaxed both arteries, mesenteric being more sensitive than pulmonary arteries and noradrenaline more sensitive than U46619-induced contractions. In conclusion, differences in the relaxant effects for all vasodilators were found depending on the artery, the vasoconstrictor used or both. However, ATP was the only drug which, regardless of the concentration or vasoconstrictor used, produced greater relaxant effects in pulmonary than in mesenteric arteries.