Constrictor actions of acetylcholine, 5-hydroxytryptamine and histamine on bovine coronary artery inner and outer muscle.

1. In bovine coronary arteries, cholinesterase staining showed an extensive cholinergic innervation at the adventitia-media junction, and some cholinesterase in the outer but not inner smooth muscle.2. Acetylcholine or methacholine caused large, atropine-sensitive contractions of outer muscle but caused little contraction of inner muscle.3. Fluorescence microscopy for monoamines and for histamine, supported by chemical assays, showed no adrenergic innervation but showed numerous fluorescent cells in the adventitia and the outer 50% of the media which stained as mast cells and contained large amounts of histamine and noradrenaline and some dopamine, but little 5-hydroxytryptamine (5-HT).4. 5-hydroxytryptamine (acting by D receptors) and histamine (acting by H(1) receptors) in high concentrations caused large contractions, of similar size, in inner and outer muscle. In given submaximal concentrations they generally caused more contraction of outer than inner muscle, particularly in the case of histamine, provided that imipramine or desipramine was present to inhibit uptake of the agents by mast cells which were present in the outer part of the artery wall.5. Without blockade of uptake, 5-HT applied to the arteries in submaximal concentrations caused less contraction of outer than inner muscle; histamine still caused significantly more contraction of outer than inner muscle.6. The findings indicate that the cholinergic constrictor nerves of these arteries, unlike adrenergic constrictor nerves of other systemic arteries, act almost solely on outer muscle of the vessel wall; and that mast cells give considerable protection against constriction by 5-HT, but little against histamine, reaching the vessel from its adventitial surface.