Pharmacological studies on internal mammary artery bypass grafts. Action of endogenous and exogenous vasodilators and vasoconstrictors.
BACKGROUND: The purpose of this experiment was four-fold: 1) to determine the effect of currently used cardiovascular drugs on internal mammary artery (IMA) vascular tone, 2) to examine IMA reactivity to autacoids and products released from aggregating platelets, 3) to compare the vascular reactivity of the right versus left IMA, and 4) to determine whether the canine IMA was an acceptable physiological model as regards its similarity to the human IMA, which is used routinely for coronary artery bypass grafting. METHODS: To study factors that modulate the tone of IMA, bypass grafts, right and left canine IMAs were studied in vitro in organ chambers (95% O(2)/5% CO(2), pH=7.4). RESULTS: Increasing concentrations (10(-9) to 10(-4M)) of the neurotransmitter acetylcholine (ACH) and the platelet-derived products adenosine diphosphate (ADP) or serotonin (5-HT) induced vasodilatation of contracted right and left IMAs. The vasodilation caused by ACH and ADP was endothelium-dependent while serotonin acted directly on the vascular smooth muscle. Histamine and bradykinin also induced IMA vasodilation, histamine via a direct action on the smooth muscle, and bradykinin through the release of nitric oxide (NO). In canine IMAs, the calcium ionophore A23187 produced endothelium-dependent vasodilation of contracted blood vessels; this vasodilation was blocked by N(G)-nitro-L-arginine (10(-4)M), a competitive inhibitor of nitric oxide synthesis from L-arginine, and by hemoglobin (10(-5)M). Dopamine, dobutamine, and papaverine induced vasodilation of the IMA regardless of the presence or absence of an intact intima, while norepinephrine induced profound IMA vasoconstriction, which was comparable to contraction to potassium ions or the constrictor peptide endothelin. CONCLUSIONS: These experiments establish a pharmacological profile of IMA and demonstrate that endogenous and exogenous compounds can significantly alter its vascular tone.