Augmentation of adenosine-induced relaxation response with hydralazine in aortic strips.
Adenosine produced a slight but concentration-dependent relaxation in rabbit aortic strips preconstricted with norepinephrine. The effect of adenosine was markedly augmented in the presence of hydralazine. On the other hand, the adenosine-induced relaxation was attenuated by 8-phenyltheophylline, but was unaffected by indomethacin, nordihydroguaiaretic acid and quinacrine, indicating that adenosine acts via purinergic receptors and that vasodilating metabolites of arachidonic acid are not involved in the relaxation. The adenosine-induced relaxation remained unaffected by S-(p-nitrobenzyl)-6-thioguanosine (NBTG) or 2'-deoxycoformycin (2'DCF), alone or combined. NBTG significantly inhibited the incorporation of [3H] adenosine, while the content of [3H] compound was increased by 2'DCF, but was unchanged by hydralazine. Hydralazine also augmented the 2-chloroadenosine-induced relaxation. These results suggest that the augmentation of adenosine-induced relaxation with hydralazine does not result from an inhibition of adenosine transport and/or adenosine deaminase. When adenosine was added, relaxation was elicited with concomitant increase in cAMP, but with no significant change in cGMP. In the presence of hydralazine, the cAMP increasing effect of adenosine was augmented, and the level of cGMP increased with adenosine. These changes in cyclic nucleotide levels might at least in part explain the augmentation of adenosine-induced relaxation with hydralazine.
Azuma
H
H
Institute for Medical and Dental Engineering, Tokyo Medical and Dental University, Japan.
Mizushima-Kasahara
K
K
Sekizaki
S
S
Ishikawa
M
M
D000241:Adenosine / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects; D000242:Cyclic AMP / Q000032:analysis; D006152:Cyclic GMP / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006830:Hydralazine / Q000494:pharmacology*; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D011817:Rabbits
D006830:Hydralazine; D000242:Cyclic AMP; D006152:Cyclic GMP; D000241:Adenosine