Cholinergic modulation of non-adrenergic, non-cholinergic relaxation in isolated, small coronary arteries from lambs

Abstract

The presence of cholinergic innervation of small coronary arteries in the lamb was investigated by measuring choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) activities and by performing in vitro experiments in a microvascular myograph to establish whether or not there is a cholinergic component in the response to electrical field stimulation (EFS). ChAT-specific activity was present in proximal coronary segments, but was significantly higher in small coronary arteries. AChE-positive ganglia and fibres were distributed within the adventitia and outer third of the media in proximal coronary segments, and dense perivascular nerve plexuses were observed in small coronary arteries. Acetylcholine induced contractions in all preparations examined and relaxations in 20% of the segments contracted with the thromboxane analogue U46619. EFS did not induce neurogenic contractions in lamb small coronary arteries. In the presence of the alpha-adrenoceptor antagonist, phentolamine, EFS caused frequency-dependent reproducible relaxations that were enhanced by the blocker of cholinergic transmission, botulinum neurotoxin. An inhibitor of AChE, physostigmine, had no significant effect on the relaxations caused by EFS, while both the muscarinic receptor antagonist, atropine, and the muscarinic M2-receptor antagonist, AFDX 116, enhanced these responses. Blockade of sympathetic neurotransmission with guanethidine or incubation with the P2-receptor antagonist, suramin, abolished the relaxations induced by EFS, whereas propranolol was without effect. Low-frequency EFS caused less relaxation in preparations activated by acetylcholine than in those contracted with U46619, while sensitivity and maximal relaxation induced by adenosine 5'-triphosphate (ATP) were not different in U46619- and acetylcholine-contracted arteries. The presence of the enzymes necessary for both biosynthesis and degradation of acetylcholine and the finding that blockers of cholinergic neurotransmission enhance EFS-induced relaxations suggest that small coronary arteries are cholinergically innervated.

Cholinesterase activity in human pulmonary arteries and veins: correlation with mRNA levels

“…Similar results were described with physostigmine in the bovine retinal and dog femoral arteries (Norel et al, 1993;Minami et al, 1989) or with neostigmine in the rabbit pulmonary artery (Altiere et al, 1994). In contrast, most of the vascular effects of ChE inhibitors were observed during vasoconstriction induced by ACh, in the monkey ciliary and cerebral arteries (Toda et al, 1997(Toda et al, , 1998, in the lamb coronary artery (Simonsen et al, 1999), in the rabbit and human pulmonary arteries (Altiere et al, 1994;Walch et al, 1997) and in some veins with embryonic origin from the digestive tube (canine portal, mesenteric and inferior vena cava; Yoshioka et al, 1988). In summary, the control of vascular tone by the ChE activities in isolated preparations may be unmasked when a direct smooth muscle response induced by ACh dominates the endothelial response.…”

Penile Arteries and Erection

“…In systemic arteries neural-released and exogenously applied ATP elicits vasoconstriction through activation of P2X-purinoceptors [130], but neurogenic relaxations sensitive to P2Y-purinoceptors have also been described in pulmonary and coronary small arteries [110, 131, 132]. In coronary small arteries, the neurogenic relaxations were also inhibited in the presence of guanethidine suggesting that ATP derived from adrenergic nerve endings mediates these relaxations [110].…”

“…obs.]. Therefore, the role of acetylcholine, as is the case for cerebral arteries [109]and coronary arteries [110], is probably a modulatory effect inhibiting noradrenaline release and enhancing the vasodilatation induced by the main neurotransmitter NO. However, the specific underlying mechanisms remain unidentified.…”

“…In coronary small arteries, the neurogenic relaxations were also inhibited in the presence of guanethidine suggesting that ATP derived from adrenergic nerve endings mediates these relaxations [110]. Low concentrations of ATP relax bovine penile small arteries, but the general purinoceptor antagonist, suramin, does not affect the non-adrenergic non-cholinergic neurogenic relaxation in this preparation [Simonsen, unpubl.…”

Effect of the effluent released from the canine internal mammary artery after intraluminal and extraluminal perfusion of acetylcholine and adenosine diphosphate

“…Previous studies have been described that the coronary arteries are supplied by cholinergic nerves that modulate a non-adrenergic and non-cholinergic relaxation in isolated small coronary arteries suggesting that acetylcholine is also able to stimulate inhibitory non-adrenergic and non-cholinergic mediators released from the perivascular neural receptor [ 6 - 8 ].…”