Endothelium‐dependent contraction induced by acetylcholine in the chicken ductus arteriosus: involvement of a cyclooxygenase‐derived TP receptor agonist

Abstract

In numerous vascular beds, acetylcholine (ACh) evokes the simultaneous release of endothelium‐derived relaxing and contracting factors (EDRF and EDCF, respectively). We aimed to determine whether ACh evokes the release of an EDCF in the chicken ductus arteriosus (DA) and to identify its nature. Isolated rings of the DA from 19‐d chicken fetuses (total incubation: 21‐d) were mounted in a myograph. Low concentrations of ACh (30 nM‐ 1 µM) elicited a relaxation, which was followed by a contraction at higher concentrations (3 μM ‐0.1 mM). Both relaxation and contraction were abolished by removal of endothelium and were sensitive to the antimuscarinic agents atropine and 4‐DAMP (M3‐receptor antagonist). ACh‐induced relaxation was impaired in the presence of the nitric oxide (NO) synthase inhibitor L‐NAME and the soluble guanylate cyclase (sGC) inhibitor ODQ. ACh‐induced contraction was impaired in the presence of the nonselective inhibitor of cyclooxygenase (COX) indomethacin, the selective COX‐1 inhibitor valeryl salicylate, and the thromboxane A2 (TP) receptor blocker SQ‐29458, whereas the response was not affected by the selective COX‐2 inhibitor nimesulide, the thromboxane synthase inhibitor furegrelate, or the H2O2 scavenger PEG‐catalase. We conclude that in the chicken DA, stimulation of muscarinic receptors by ACh induces an endothelium‐dependent relaxation followed by an endothelium‐dependent contraction. The relaxation involves the NO‐sGC pathway, whereas the contraction involves a COX‐1 product that stimulates TP receptors.Supported by "Fundaci ónde Investigación Médica Mutua Madrileña".