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Sympathetic Control of Carotid Body Sympathoexcitatory Reflex Responsiveness in Spontaneously Hypertensive Rats
Author(s) -
Felippe Igor,
Paton Julian
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2021.35.s1.03247
Subject(s) - phenylephrine , baroreflex , hyperreflexia , medicine , sympathetic nervous system , reflex , carotid body , endocrinology , heart rate , anesthesia , stimulation , blood pressure
Previous studies have demonstrated that the integrity of the carotid bodies (CBs) is essential for the development and maintenance of hypertension via exacerbated sympathetic drive. CBs of spontaneously hypertensive rats (SHR) exhibit both increased tonicity and hyperreflexia. However, what drives this CB hyper‐excitability is not fully understood. We hypothesised that CB hyperreflexia is mediated by its sympathetic innervation, which originates from the superior cervical ganglion (SCG). Experiments were carried out in Wistar and SH rats (60‐80g) using the in situ working heart‐brainstem preparation (WHBP). Phrenic and thoracic sympathetic nerves, heart rate and perfusion pressure were recorded and the chemoreflex activated using NaCN (50‐100µL, 0.04%). Drug infusions into the CB were made via a cannula placed in the internal carotid artery with its tip juxta‐positioned to the carotid body artery. To assess if the SCG modulates the chemoreflex, we stimulated the SCG electrically. This enhanced the chemoreflex evoked sympathoexcitation in both rat strains by 40‐50% (P<0.05); this hyperreflexia was not different between rat strains and restricted to the chemoreflex sympathetic response with no obvious change in heart rate, perfusion pressure or phrenic nerve responses. The SCG evoked hyperreflexia of the sympathetic chemoreflex was prevented by Tamsulosin, an alpha1‐adrenoceptor antagonist, applied to the CB. To mimic the effect of SCG stimulation, we applied phenylephrine (an alpha1 adrenoceptor agonist) to the CB, whichenhanced the chemoreflex sympathoexcitation by 33% (P<0.05). Next, we ascertained whether there was any endogenous modulation of the chemoreflex by the SCG in SH rats. Both SCG ganglionectomy and alpha1 adrenoceptor antagonism reduced the chemoreflex evoked sympathoexcitation (P<0.01). To equivalent levels observed in Wistar rats. Notably, respiratory‐sympathetic coupling was also reduced by alpha1 adrenoceptor antagonism of the CB in SH rats. Immunohistochemistry showed positive co‐localisation of alpha1A‐ and alpha1B‐ adrenoreceptors on both glomus cells and blood vessels within the CB. We conclude, sympathetic activity modulates CB reflex sensitivity via alpha1‐adrenoreceptors and this appears to be a mechanism underpinning the pathological hyperreflexia of the CB in SH rats. We propose that a positive feedback loop whereby CB activity drives the sympathetic nervous system and increased sympathetic innervation of the CB causes its sensitisation is a pivotal mechanism for the development of hypertension. Our data support the SCG as a novel target for controlling blood pressure in hypertension.