Endothelium-dependent relaxations to adenosine in juvenile rabbit pulmonary arteries and veins.
We studied the actions of adenosine and its analogues 5'-(N-ethylcarboxamido)-adenosine (NECA) and N6-cyclohexyladenosine (CHA) in pulmonary vessels isolated from juvenile rabbits. Pulmonary arteries relaxed in a concentration-dependent fashion to all three compounds. Pretreatment with the methylxanthine 8-p-sulfophenyltheophylline shifted the concentration-response curves to adenosine and NECA rightward, indicating that the vasodilator effects were mediated by the adenosine receptor. The order of potency of adenosine compounds was NECA > adenosine > CHA, indicating that the A2-receptor mediates relaxations to adenosine in rabbit pulmonary arteries. Endothelium rubbing attenuated relaxations to adenosine at concentrations of < or = 3 x 10(-7) M and to all NECA concentrations. Inhibition of nitric oxide synthase with NG-nitro-L-arginine (L-NNA) similarly attenuated relaxations at concentrations of < or = 3 x 10(-7) M for adenosine and < or = 3 x 10(-8) M for NECA. With the use of the same methods, a substantial endothelial contribution was additionally observed in pulmonary veins to the vasodilator effects of NECA. We conclude that adenosine, and the more specific A2-receptor agonist NECA, dilate pulmonary arteries and veins isolated from young rabbits via a mechanism that is partially dependent on endothelium-derived nitric oxide.
Steinhorn
R H
RH
Department of Pediatrics, State University of New York, Buffalo 14214.
Morin
F C
FC
Van Wylen
D G
DG
Gugino
S F
SF
Giese
E C
EC
Russell
J A
JA
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D019830:Adenosine-5'-(N-ethylcarboxamide); D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000502:physiology*; D066298:In Vitro Techniques; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D019001:Nitric Oxide Synthase; D019335:Nitroarginine; D011651:Pulmonary Artery / Q000187:drug effects / Q000502:physiology*; D011667:Pulmonary Veins / Q000187:drug effects / Q000502:physiology*; D011817:Rabbits
D019335:Nitroarginine; D019830:Adenosine-5'-(N-ethylcarboxamide); C027513:N(6)-cyclohexyladenosine; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D000241:Adenosine