Barbiturate inhibition of endothelium-dependent dilatation of blood- and Krebs-perfused rat tail arteries.

Rat tail artery segments were cannulated both ends, immersed in an organ bath filled with Krebs solution, and perfused at a constant 3 ml/min with Krebs solution from a reservoir or arterial blood from a donor conscious rat. Donor rats had chronic indwelling exteriorized silastic cannulas in a carotid artery and jugular vein. Blood withdrawn from the carotid artery returned to the donor rat via the jugular vein cannula after perfusing the tail artery segment. Arteries were constricted and perfusion pressure increased by infusing noradrenaline into the perfusate. In Krebs perfused arteries vasodilator responses were obtained to acetylcholine (ACh) and sodium nitroprusside (NP) infused for 1 min at 10(-6) M. The addition of the barbiturates, 'Inactin' (5-ethyl-5-(1-methylpropyl)-2-thiobarbiturate) and pentobarbitone, at 10, 30 and 100 micrograms/ml progressively inhibited responses to ACh but not to NP. Pentobarbitone 30 micrograms/ml also significantly inhibited responses to 3 X 10(-7) M of the calcium ionophore A23187, shifted the dose-response curve for ACh to the right and suppressed the maximum ACh response. Vasoconstrictor responses were also obtained by periarterial stimulation of the sympathetic nerves at 5 Hz for 5 s every 2 min. These responses were markedly inhibited by ACh (10(-5) M) and this inhibition was not affected by Inactin 100 micrograms/ml. In arterial segments perfused with blood from a donor conscious rat, ACh infused for 1 min at a rate calculated to produce a concentration of 10(-4) M in the blood perfusate at the site of infusion, decreased tail artery perfusion pressure.(ABSTRACT TRUNCATED AT 250 WORDS)