Sympathetic control of carotid body excitability in hypertension: A preclinical study

Previous studies have demonstrated that the integrity of carotid bodies is essential for the development and maintenance of hypertension via exacerbated sympathetic drive. Carotid bodies of spontaneously hypertensive (SH) rats exhibit both hypertonicity and hyperreflexia (i.e., hyper-excitability), which is not fully understood. Our aim was to test whether carotid body hyper-excitability is mediated by its sympathetic innervation. Chemoreflex was activated (NaCN 50-100 μL, 0.04%) in Wistar and SH rats in situ before and after: 1) electrical stimulation (ES; 30 Hz, 2 ms, 10 V) of the superior cervical ganglion (SCG), which innervates the carotid body; 2) unilateral resection of the SCG (SCGx); and 3) carotid body injections of α1-adrenoreceptors agonist (phenylephrine, 50 μL, 1 mM) in Wistar and antagonist (tamsulosin, 50 μL, 1 mM) in SH rats. Blind whole-cell patch-clamp recordings of chemoreceptive petrosal ganglion (PG) Neurones and in vivo radio-telemetric recordings were also carried out to evaluate the effect of SCGx on carotid body excitability of SH rats. ES of the SCG enhanced carotid body-evoked sympathoexcitation by 40-50% (P<0.05) with no difference between rat strains. This effect was prevented by tamsulosin injected via the internal carotid artery and mimicked by phenylephrine; the latter enhanced the chemoreflex sympathoexcitation by 33% (P<0.05). Unilateral SCGx attenuated the carotid body-evoked sympathoexcitation in SH rats (62%; P<0.01) but was without effect in Wistar rats; it also abolished the ongoing firing of chemoreceptive PG neurones of SH rats, which became hyperpolarised. In conscious SHR, the chemoreflex was attenuated, and systolic blood pressure fell by 16 ± 4.85 mmHg. Immunohistochemistry showed positive expression of α1A- and α1B- adrenoreceptors on both glomus cells and blood vessels within the carotid body. The sympathetic innervation of the carotid body is tonically activated and sensitises the carotid body of SH rats but not Wistar rats. Furthermore, sensitisation of carotid body-evoked sympathoexcitation appears to be mediated by α1-adrenoreceptors located either on the vasculature and/or glomus cells. Our data support the SCG as a novel target for controlling blood pressure in hypertension

Name thesis:degree_name

PhD

Level thesis:degree_level

Doctoral

Discipline thesis:degree_discipline

Biomedical Science

Grantor dc:publisher

ResearchSpace@Auckland

Year dc:date.issued

2022

Author dc:creator

• Felippe, Igor Simoes Assuncao

Advisors dc:contributor.advisor

• Paton, Julian
• McCormick, Daniel
• Freestone, Peter
• Guild, Sarah-Jane
• McBryde, Fiona

Statement dc:rights

• Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Licence dc:rights.uri

• https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm

Handle dc:identifier.uri

https://hdl.handle.net/2292/59348

OAI identifier oai:identifier

oai:researchspace.auckland.ac.nz:2292/59348