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 GABA A receptors in retinal ganglion cells (RGCs) and relaxing blood vessels via eNOS–NO, with GABA binding to GABA B receptors on retinal capillary endothelial cells. Conclusion and Implications α7‐nAChR activation causes vasorelaxation of retinal capillaries.