Effects of Na-K-ATPase inhibition on catecholamine reactivity in rat pulmonary artery.
The objective of this study was to determine the effects of Na-K-adenosinetriphosphatase (ATPase) inhibition on aspects of vascular reactivity in rat pulmonary artery, including resting tone and catecholamine reactivity, loss of reactivity to repeated catecholamine stimulation, and contraction-relaxation kinetics. The effect of ATPase inhibition on resting tone and catecholamine reactivity was determined by comparing the responses to 10(-4) and 10(-3) M ouabain (Oua-4, Oua-3), 10(-4) M tyramine, and 10(-6) M norepinephrine (NE) pre- and postouabain. Loss of responsiveness to NE was induced by repeated cumulative doses of NE (NE I, NE II) with 60 min between exposures. ATPase inhibition was superimposed on this loss of reactivity by 1) administration of Oua-4 or Oua-3 15 min before NE II, 2) incubation in K(+)-free solution 15 min before NE II, and 3) incubation in K(+)-free solution 15 min before NE I for the entire protocol. The effect of ATPase inhibition on the response pattern after repetitive dosing with phenylephrine (PE) and KCl was also determined. To correlate ATPase activity with the loss of reactivity after catecholamine stimulation, we measured ATPase activity (86Rb uptake) at different time points after repeated NE administration. The effect of ATPase inhibition on contraction-relaxation rates after catecholamine stimulation was determined by analyzing the response to repeated single doses of NE in normal salt solution and after incubation in K(+)-free solution.(ABSTRACT TRUNCATED AT 250 WORDS)
Cutaia
M
M
Veterans Affairs Medical Center, Providence, Rhode Island 02908.
Rudio
K
K
D000818:Animals; D002395:Catecholamines / Q000494:pharmacology*; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D010042:Ouabain / Q000494:pharmacology; D011651:Pulmonary Artery / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013618:Tachyphylaxis; D014439:Tyramine / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
D002395:Catecholamines; D010042:Ouabain; D000254:Sodium-Potassium-Exchanging ATPase; D009638:Norepinephrine; D014439:Tyramine