Inhibition of vasoactive amine induced contractions of vascular smooth muscle by hydrogen peroxide in rabbit aorta.
OBJECTIVE
The aims were to investigate the effects of H2O2 on arterial contractions induced by vasoactive amine agonists and a high concentration of potassium ions (high K+) in vitro and to explore the possible underlying mechanism(s) involved.


METHODS
Isometric tension of rabbit isolated aortic strips was measured and the effects of pretreatment with H2O2 on contractions induced by phenylephrine and high K+ were compared. The effects of H2O2 on precontracted strips were determined in the presence and absence of the aortic endothelium and compared with those of acetylcholine.


RESULTS
The tension developed in response to an agonist was expressed as a percentage of the contraction induced by high K+ (64.7 mM) superfusion. Pretreatment with 300 microM H2O2 reduced the mean phenylephrine (0.3 microM) induced contraction from 96.2(SEM 1.4) to 61.8(2.8)%; the effect was stable and reversed by washing out the H2O2. Hydrogen peroxide relaxed phenylphrine precontracted strips with and without endothelium but it showed no relaxant effect when the strips were precontracted by high K+, whereas acetylcholine (1 microM) induced transient relaxation of high K+ precontracted strips by 27.8(2.9)%. The relaxant effect of H2O2 was not affected by pretreatment with indomethacin (a cyclo-oxygenase inhibitor), desferrioxamine (a hydroxyl radical scavenger), or diphenylphenylenediamine (a lipophilic antioxidant).


CONCLUSIONS
H2O2 inhibits vasoactive amine induced contractions of the vascular smooth muscle of rabbit aorta in vitro without affecting voltage dependent Ca2+ influx or contractile machinery. The mechanism responsible for its inhibitory effects may be related to impairments of the cellular signalling reactions initiated by the agonists.
Iesaki
T
T
Juntendo University School of Medicine, Tokyo, Japan.
Okada
T
T
Yamaguchi
H
H
Ochi
R
R
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001011:Aorta; D003676:Deferoxamine / Q000494:pharmacology; D003864:Depression, Chemical; D004730:Endothelium, Vascular / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D010655:Phenylenediamines / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology*; D011817:Rabbits
D000975:Antioxidants; D010655:Phenylenediamines; D010656:Phenylephrine; D006861:Hydrogen Peroxide; C004845:N,N'-diphenyl-4-phenylenediamine; D003676:Deferoxamine; D000109:Acetylcholine; D011188:Potassium; D007213:Indomethacin