Cholinergic control of human and animal pulmonary vascular tone.

ABSTRACT

The regulation of pulmonary vascular tone by acetylcholine (ACh) involves the activation of different subtypes of muscarinic receptors as well as the cholinesterase activities which are responsible for ACh degradation. Most of the studies on the cholinergic control of the pulmonary vascular tone have been performed in vessels derived from animals. The ability of ACh to induce pulmonary vasoconstriction is species dependent. In vessels derived from sheep lung, ACh induced contractions in veins but not in arteries whereas in human pulmonary vessels the reverse was observed. The subtype(s) of the muscarinic receptors involved in the pulmonary vasoconstrictions is also dependent on the species which are studied. M1 receptors are implicated in the rabbit pulmonary vasoconstrictions, M3 in humans, whereas M1 and M2 receptors are involved in the dog. The cholinesterases are implicated in the vasoconstriction produced by ACh in human and rabbit pulmonary arteries. However, in these studies while acetylcholinesterase (EC 3.1.1.7) and butyrylcholinesterase (EC 3.1.1.8) activities were detected in human vessels only acetylcholinesterase activity was found in rabbit vessels. The endothelium-dependent relaxation induced by ACh has been reported in isolated pulmonary vessels from different animals including man. However, the muscarinic receptors involved in the ACh-induced vasodilatation of rat and rabbit pulmonary artery are of the M3 subtype while those characterized in the human pulmonary artery are of the M3 and M1 subtypes. Together these results concerning the cholinergic control of the pulmonary vascular tone indicate that extrapolation of the data obtained in animal models to human vessels requires some caution. In addition, there is considerable evidence to demonstrate that ageing may modify cholinergic responses. However, little information is available concerning the pulmonary vascular bed during ageing.