Alpha 7-nicotinic cholinoceptor regulation of pericyte-containing retinal capillaries.

ABSTRACT

BACKGROUND AND PURPOSE: Local blood flow regulation relies on the coordination between neurons and pericyte-containing capillaries. Pericyte relaxation and contraction are influenced by vasoactive substances and regulated by neurotransmitters. α7 nicotinic acetylcholine receptors (α7-nAChRs), involved in the regulation of vascular function and inhibitory γ-aminobutyric acid (GABA) systems, have neuroprotective effects against CNS diseases. Although α7-nAChRs are found throughout the retina, their contribution to the retinal capillary tone remains unknown. Here, we investigated the neurovascular coupling mechanism underlying α7-nAChR-mediated retinal capillary tone regulation. EXPERIMENTAL APPROACH: Changes in capillary diameter and pericyte transverse diameter during drug perfusion were observed using differential interference contrast (DIC) microscopy, to help elucidate signalling pathways underlying α7-nAChR-mediated regulation of capillary blood flow at the whole retinal level. Patch clamp technique was used to investigate α7-nAChR-mediated regulation of the GABA synaptic circuit. Immunofluorescence was used to explore the expression of α7-nAChRs and GABA receptors. KEY RESULTS: Activating α7-nAChRs on the endothelial cell membrane caused perinuclear accumulation of endothelial nitric oxide synthase (eNOS), resulting in dilated retinal capillaries and pericytes via the nitric oxide synthase (NOS)/nitric oxide (NO)/guanosine 3',5'- monophosphate (cGMP) signalling pathway. Neuronal α7-nAChR activation directly relaxed retinal capillaries and pericytes via a neurovascular coupling mechanism. α7-nAChR also increased the vesicular release of GABA, possibly promoting the release of NO by binding to GABAA receptors in retinal ganglion cells (RGCs) and relaxing blood vessels via eNOS-NO, with GABA binding to GABAB receptors on retinal capillary endothelial cells. CONCLUSION AND IMPLICATIONS α7-nAChR activation causes vasorelaxation of retinal capillaries.