Role of muscarinic cholinergic transmission in Edinger-Westphal nucleus-induced choroidal vasodilation in pigeon

Activation of the parasympathetic ciliary ganglion input to the choroid cau ses increases in choroidal blood flow. We examined the role and the type of muscarinic receptors within the choroid that are involved in these increas es in choroidal blood now, using electrical stimulation of the nucleus of E dinger-Westphal (EW) to activate the ciliary ganglion input to choroid in k etamine anesthetized pigeons Baseline choroidal blood flow and its ES-evoke d increases measured as peak and total (area under the curve) responses wer e determined using laser Doppler flowmetry. The EW-evoked responses were re duced dose-dependently after administration of 4-diphenyl-acetoxy-N-methylp iperedine (4-DAMP), a relatively selective antagonist of M3 type muscarinic receptors, with a maximal mean decrease of 86% (peak response) and 93% (to tal response) at a dose of 10 mu g kg(-1) i.v. without a significant effect on baseline choroidal blood flow, heart rate or systemic arterial blood pr essure. Atropine, a non-selective antagonist of muscarinic receptors, decre ased the EW-evoked responses to a lesser extent than 4-DAMP after intraveno us administration of 1 mg kg(-1) (by 67% for peak response and by 53% for t otal response) or topical administration of a 5% solution (by 41 % for peak response and by 62 % for total response), both of which increased heart ra te and systemic arterial blood pressure without a consistent effect on base line choroidal blood flow, in contrast, himbacine (i.p. 10 mu g kg(-1)), a relatively selective antagonist of M2 type muscarinic receptors, increased the EW-evoked parasympathetic cholinergic vasodilation (by 93% for the peak response and by 142% for the total response) without a significant effect on heart rate, systemic arterial blood pressure or baseline choroidal blood flow. The results of our study suggest a major role of M3 type muscarinic receptors in the EW-evoked increases in choroidal blood flow, Based on Endi ngs that the ciliary ganglion input to choroid does not synthesize nitric o xide but inhibitors of NO production do block EW-evoked choroidal vasodilat ion, it seems likely that the M3 receptors acted on by 4-DAMP are present o n choroidal endothelial cells and mediate choroidal vasodilation via stimul ation of endothelial release of nitric oxide. In contrast, M2 muscarinic re ceptors may play a presynaptic role in downregulating EW-evoked parasympath etic cholinergic vasodilation in avian choroid. (C) 2000 Academic Press.