Acetylcholine-Induced Contractions in the Perforating Branch of the Human Internal Mammary Artery: Protective Role of the Vascular Endothelium

Abstract

The effect of acetylcholine (ACh) on the isolated, nonprecontracted perforating branch of the human internal mammary artery (HIMA) was investigated. ACh induced concentration-dependent contractions of nonprecontracted rings with denuded endothelium (pEC₅₀ = 6.72 ± 0.02, E_max = 88.8% of contractions induced by phenylephrine, 10^–5 mol/l) and was without effect on arterial segments with intact endothelium. An inhibitor of nitric oxide synthase, N^G-monomethyl-L-arginine (L-NMMA), or indometacin, a cyclooxygenase inhibitor, had no effect on acetylcholine-induced contractions of rings of the perforating branch of HIMA with denuded endothelium (pEC₅₀ = 6.76 ± 0.03 and 6.62 ± 0.05, respectively). In the presence of indometacin, ACh did not evoke contractions of arterial segments with intact endothelium. In contrast, in the same type of preparations ACh induced contractions in the presence of L-NMMA (E_max = 34%). The muscarinic receptor antagonists atropine (no selectivity), pirenzepine (M₁), methoctramine (M₂), and p-fluoro-hexahydro-sila-difenidol (M₁/M₃) competitively antagonized the response to ACh. The pA₂ values were 9.60 ± 0.10, 6.99 ± 0.02, 6.37 ± 0.17, and 8.02 ± 0.06, respectively. In conclusion, the results obtained indicate that secretion of nitric oxide from vascular endothelium may protect the perforating branch of HIMA against the contractile effects of ACh. On the basis of differential antagonist affinity, it can be suggested that the muscarinic receptors involved in the ACh-induced contractions of the isolated perforating branch of the HIMA are predominantly of the M₃ subtype.