Loss of nitric oxide release in passively sensitized guinea-pig aorta with purified immunoglobulin G1.
BACKGROUND
Vascular hyperresponsiveness can be reproduced by in vitro passive sensitization of isolated aorta with immunoglobulin G1 (IgG1) taken from ovalbumen-sensitized BFA guinea-pig.


OBJECTIVE
The aim of the present work was to investigate the role of nitric oxide in the sensitization-induced alteration of the contractile and relaxant responses of guinea-pig aorta to noradrenaline (NA) and acetylcholine (ACh), respectively.


METHODS
Cumulative concentration-response curves to NA or ACh were established before and after IgG1 sensitization and then after successive treatments.


RESULTS
IgG1 in vitro passive sensitization of aorta caused a significant hyperreactivity to NA and completely inhibited the relaxation to ACh. After sensitization, the addition of an intact aortic ring (with endothelium) in the organ chamber restored the maximal response to NA and ACh close to control but was ineffective in the presence of hemoglobin. The restoration of the control reactivity to NA was also inhibited in the presence of L-NAME or when the added aortic ring was endothelium-denuded. Moreover, L-arginine, a nitric oxide (NO) precursor, was able to restore the control reactivity to NA.


CONCLUSIONS
The present results show that IgG1 in vitro sensitization induced a loss of NO release from the vascular endothelium. This loss of NO probably plays a great role in vascular hyperreactivity by increasing the contractile response and decreasing the relaxant response to mediators and would be a component of allergic diseases pathogenesis.
Jondet
A
A
Laboratoire de Physiologie Pharmacodynamie et Thérapeutique, jeune équipe associée INRA d'Immuno-Endocrinologie Cellulaire et Moléculaire, Ecole Nationale Vétérinaire, Nantes, France.
Gogny
M
M
Vu
A T
AT
Blin
M
M
Bidon
J C
JC
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D006168:Guinea Pigs; D007074:Immunoglobulin G / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology
D007074:Immunoglobulin G; D009569:Nitric Oxide; D000109:Acetylcholine; D009638:Norepinephrine