Ligamentum Arteriosum: An Innervated and Contractile Muscular Structure

Abstract

IntroductionThe ligamentum arteriosum (LA) is generally described as a mere fibrotic remnant of the embryonic bypass (ductus arteriosus) from the pulmonary trunk to the aortic arch, obliterating soon after childbirth. There have been anecdotal and contradictory reports on this speculated morphological change. This study set out to elucidate the morphology, innervation, neurochemistry and function of LA.MethodLA of human, pig, wild‐type and appropriate transgenic reporter mouse strains were studied using routine and special histological staining methods, single‐ and double‐immunofluorescence labeling using antibodies directed against structural markers such as α‐smooth muscle actin (αSMA) and protein gene product 9.5 (PGP 9.5), against neuropeptides such as neuropeptide Y (NPY), vasoactive intestinal peptide (VIP), substance P (SP), and calcitonin gene‐related peptide (CGRP), and against transmitter synthesizing enzymes such as tyrosine hydroxylase (TH; noradrenergic), choline acetyltransferase (ChAT; cholinergic), and nitric oxide synthase (NOS). Additionally, pig and mice LA were investigated using transmission electron microscopy (TEM). Organ bath experiments subjected pig LA to increasing cumulative doses of exogenous noradrenalin (NA), ɑ1‐adrenergic antagonists (tamsulosin and prazosin) and varying Hz of electrical field stimulation.ResultsContrary to a canonical ligament, the LA was mainly made up by αSMA‐positive cells in all three species. TEM confirmed the presence of smooth muscle cells with caveolae, mmyofilaments’, dense bands etc. within the LA. The ligament received a noticeable amount of noradrenergic (TH, NPY) and sensory (CGRP, SP) but no cholinergic innervation in all three species investigated. The LA exhibited a dose‐ and frequency‐dependent contraction in response to cumulative doses of exogenous NA and electrical field stimulation respectively. Furthermore, NA pre‐contracted LA relaxed to baseline upon administration of ɑ1‐adrenergic antagoniststs (tamsulosin and prazosin).ConclusionThe LA may not function in its original capacity as a foetal shunt but still retains smooth muscles cells until senescence. Ultra‐structurally, the presence of myofilaments, dense bodies and dense bands on smooth muscle cells (SMC) observed within the LA are findings compatible with the apparatus responsible for contraction in SMC. Furthermore, the presence of numerous mitochondria, a cellular organelle, and a potential site of calcium accumulation for smooth muscle contraction, observed within the LA may play a role in its contractility. Immunoreactivity to TH‐, NPY‐, SP‐, and CGRP‐ is suggestive of sympathetic and sensory innervation within the LA. Additionally, dose‐response contractility and relaxation of pre‐contracted LA to exogenous NA and ɑ1‐adrenergic antagonists in organ bath experiments suggests activity of ɑ1‐adrenoceptors. Conclusively, it is evident that LA is made up of contractile SMC with noradrenergic and sensory innervation. Its contractility may influence the compliance or impedance of the two major vascular segments to which the LA is attached.