HN-10200 causes endothelium-independent relaxations in isolated canine arteries.
HN-10200, a nonselective inhibitor of phosphodiesterase, has positive inotropic and vasodilator activity. The present study was designed to determine the role of endothelium in causing relaxation to HN-10200 in isolated canine femoral and basilar arteries. Rings with and without endothelium were suspended for isometric tension recording in Krebs-Ringer bicarbonate solution bubbled with 94% O2, 6% CO2 (t = 37 degrees C; pH = 7.4). HN-10200 and another nonselective phosphodiesterase inhibitor, 3-isobutyl-1-methyl-xanthine (IBMX), caused similar concentration-dependent relaxations in femoral arteries with and without endothelium. In femoral arteries without endothelium, HN-10200 and IBMX significantly augmented relaxations to prostacyclin, but did not affect relaxations to a nitric oxide donor 3-morpholinosydnonimine (SIN-1) or endothelium-derived relaxing factor (EDRF) released by bradykinin. In basilar arteries, relaxations to HN-10200 were augmented by the removal of endothelium, whereas relaxations to IBMX were not affected. Relaxations to prostacyclin, SIN-1, and EDRF were not affected by the presence of phosphodiesterase inhibitors. The results of the present study suggest that HN-10200 causes endothelium-independent relaxations. In addition, it may augment relaxations to prostacyclin but does not affect relaxations to EDRF.
Cosentino
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F
Department of Anesthesiology, Mayo Clinic Foundation, Rochester, Minnesota 55905.
Schirger
A
A
Katusić
Z S
ZS
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D001488:Basilar Artery / Q000187:drug effects; D004285:Dogs; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D005263:Femoral Artery / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology*; D009126:Muscle Relaxation / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009569:Nitric Oxide; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*
C077127:HN 10200; D007093:Imidazoles; D010726:Phosphodiesterase Inhibitors; D011725:Pyridines; D009569:Nitric Oxide; D015056:1-Methyl-3-isobutylxanthine