Predominant role for nitric oxide in the relaxation induced by acetylcholine in cat cerebral arteries.
The possible role of nitric oxide (NO) and other endothelial relaxant factors in the vasodilation induced by acetylcholine (ACh) in isolated segments of cat cerebral arteries was analyzed by using the following treatments: 1) the blockers of cyclo- and lipoxygenase, indomethacin and 5,8,11,14-eicosatetraynoic acid; 2) the NO inactivators, phenidone, hydroquinone and oxyhemoglobin; 3) the inhibitors of NO synthesis, NG-nitro-L-arginine methyl ester and NG-monomethyl-L-arginine; 4) the blockers of sodium pump activity, ouabain and K(+)-free medium; and 5) the antagonist of K+ channels, 4-aminopyridine (4-AP). A comparative study between the relaxant actions of exogenous NO and ACh was also performed. The most relevant results obtained were: 1) cat cerebral arteries are very sensitive to the endothelial effects of ACh, as well as to the exogenous NO; 2) ACh-induced endothelium-dependent dilatation is not affected by indomethacin and 4-AP, partially inhibited by 5,8,11,14-eicosatetraynoic acid, phenidone, hydroquinone, oxyhemoglobin and NG-nitro-L-arginine methyl ester and abolished by NG-monomethyl-L-arginine; 3) this latter effect is selectively antagonized by L-arginine, suggesting that the inhibition of NO synthase may be enough to abolish relaxation to ACh; and 4) sodium pump blockade abolished endothelial but not exogenous NO effects. From these results, we conclude that ACh-induced relaxation in these vessels can be entirely mediated by the release of endothelial NO. Although other endothelial factors cannot be discarded, their possible contribution to ACh-evoked relaxation is likely negligible.
Alonso
M J
MJ
Departamento de Farmacología y Terapéutica, Facultad de Medicina Universidad Autónoma de Madrid, Spain.
Salaices
M
M
Sanchez-Ferrer
C F
CF
Marin
J
J
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D002415:Cats; D002536:Cerebral Arteries / Q000187:drug effects; D004347:Drug Interactions; D005260:Female; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009566:Nitrates / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D017942:Nitric Acid; D009569:Nitric Oxide / Q000378:metabolism* / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects; D000254:Sodium-Potassium-Exchanging ATPase / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*
D009566:Nitrates; D015221:Potassium Channels; D009569:Nitric Oxide; D017942:Nitric Acid; D000254:Sodium-Potassium-Exchanging ATPase; D000109:Acetylcholine