Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2021) 77 P175 | DOI: 10.1530/endoabs.77.P175

SFEBES2021 Poster Presentations Metabolism, Obesity and Diabetes (78 abstracts)

Pressure from pericytes: angiotensin II induced neuropathic pain development as a complication of hypertension

Lydia Hardowar 1,2 , Matt Sheavyn 1 , Philip McTernan 1 , Dave Bates 2 & Richard Hulse

1Nottingham Trent University, Nottingham, United Kingdom; 2University of Nottingham, Nottingham, United Kingdom

The renin angiotensin system (RAS) is targeted as means of medical intervention for hypertensive associated complications of stroke, heart failure and obesity. Ultimately, the inhibition of Angiotensin II(ANGII)/Angiotensin II type 1 (AT1) receptor complex has been key in reducing raised blood pressure. Diabetic neuropathic pain (NP) is highly prevalent in the United Kingdom, associated with an increasingly aged population. There is growing acknowledgment that the vascular component with the central nervous system is attributable to NP development through diminished blood flow in the somatosensory system. Alterations in vascular tone in neuropathology are in part modulated by pericyte regulation of capillary dynamics. Our preliminary work has identified AT1-positive pericytes, a population of contractile cells abluminally positioned on small capillaries, within spinal cord (SC) nervous tissue. Here it is hypothesised that ANGII signalling in pericytes impedes capillary function and consequent blood flow to drive NP phenotypes. Our initial studies in vitro demonstrate that in mouse SC NG2-positive pericytes ANGII (100nM) induces increased intracellular calcium response (*P < 0.016, n = 6, post-natal day7). In vivo studies demonstrate that an hour post intrathecal (i.t.) ANGII (100nM, n = 15) administration, mice develop hypersensitivity to mechanical (****P < 0.0001) and thermal (**P < 0.004) sensory stimuli tests compared to vehicle treated group (PBS, n = 9). To support pericyte activation within the dorsal horn, fluorescently stained paraformaldehyde-fixed SC indicated an increased proportion of constricted CD31-vessels associated with NG2-pericytes 30-minute post i.t. ANGII injection vs vehicle (*P < 0.039). Co-administration of i.t. Losartan with ANGII reduced hypersensitivity to pain compared to ANGII alone (*P < 0.01) 1-hour post-dose, while returning to basal level after 24 hours. These studies highlight an ANGII dependent modulation of pericyte vasocontractility via AT1 signalling in the SC that is a contributing factor in NP development. This work highlights that the modulation of AT1 in the SC maybe a putative candidate to treat diabetic NP.

Volume 77

Society for Endocrinology BES 2021

Edinburgh, United Kingdom
08 Nov 2021 - 10 Nov 2021

Society for Endocrinology 

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