Acetylcholine induces vasodilatation in the rabbit isolated heart through the release of nitric oxide, the endogenous nitrovasodilator.
1. Acetylcholine (ACh, 0.03-3.0 microM) induced a dose-dependent vasodilatation in the isolated Langendorff-perfused heart of the rabbit. The vasodilatation was mimicked by exogenous nitric oxide (NO, 0.045-4.5 nmol). 2. There was no detectable vascular relaxing activity in the cardiac effluent when these concentrations of ACh or NO were injected through the heart, even in the presence of an infusion of superoxide dismutase (SOD). 3. Acetylcholine (0.03-3.0 microM), however, induced the release into the cardiac effluent of a material which produced a chemiluminescent signal when reacted with ozone, a response which could be mimicked with exogenous NO (0.045-4.5 nmol) injected through the heart. 4. The effects of ACh, but not those of NO, were antagonized by atropine (2 microM). Prostacyclin (1 microM) injected through the heart induced vasodilatation without the release of a biologically active or chemiluminescent material. 5. During passage through the heart, greater than 99% of the biological activity of exogenous NO disappeared, whereas there was approximately 50% reduction of its chemiluminescent response. This indicates complete transformation into a mixture containing approximately 50% NO2- and 50% of other non-chemiluminescent material(s), presumably NO3-. 6. This study suggests that ACh induces endothelium-dependent vasodilatation in the coronary circulation through the release of the endogenous nitrovasodilator, NO, which is rapidly converted to NO2- and NO3-.
Amezcua
J L
JL
Wellcome Research Laboratories, Beckenham, Kent.
Dusting
G J
GJ
Palmer
R M
RM
Moncada
S
S
D000109:Acetylcholine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D011464:Epoprostenol / Q000494:pharmacology; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D008163:Luminescent Measurements; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D011817:Rabbits; D012977:Sodium Nitrite / Q000494:pharmacology; D014664:Vasodilation
D009569:Nitric Oxide; D011464:Epoprostenol; D012977:Sodium Nitrite; D000109:Acetylcholine