Pulmonary versus systemic effects of vasodilator drugs: an in vitro study in isolated intrapulmonary and mesenteric arteries of neonatal piglets.
The ability of several vasodilators to inhibit the responses to noradrenaline and U46619 (a thromboxane A2 analog) in isolated pulmonary and mesenteric arteries of neonatal piglets was compared. In pulmonary arteries, acetylcholine produced endothelium-dependent relaxations (pIC50 = about 6.8) while, in mesenteric arteries, a relaxant (< or = 10(-7) M) or a contractile response (> or = 10(-6) M) was observed. Sodium nitroprusside produced relaxant effects in pulmonary and mesenteric arteries contracted by noradrenaline (pIC50 = 6.6 and 6.0, respectively) and U46619 (pIC50 = 5.4 and 6.7, respectively). ATP induced an endothelium-independent relaxation in pulmonary arteries (pIC50 = 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 E1 induced a contractile effect whereas, at higher concentrations, a relaxant response was observed. The alpha-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 (pIC50 = 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.
Pérez-Vizcaíno
F
F
Department of Pharmacology, School of Medicine, Universidad Complutense, Madrid, Spain.
Villamor
E
E
Moro
M
M
Tamargo
J
J
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000818:Animals; D000831:Animals, Newborn; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects*; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology*; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology*; D011651:Pulmonary Artery / Q000187:drug effects*; D013552:Swine; D013928:Thromboxane A2 / Q000031:analogs & derivatives* / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology*
D011450:Prostaglandin Endoperoxides, Synthetic; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D009638:Norepinephrine