The sympathetic nervous system exacerbates carotid body sensitivity in hypertension

Abstract

Aims The carotid bodies (CB) of spontaneously hypertensive (SH) rats exhibit hypertonicity and hyperreflexia contributing to heightened peripheral sympathetic outflow. We hypothesized that CB hyperexcitability is driven by its own sympathetic innervation. Methods and results To test this, the chemoreflex was activated (NaCN 50-100 µL, 0.04%) in SH and Wistar 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 CB; 2) unilateral resection of the SCG (SCGx); 3) CB injections of an α1-adrenergic receptor agonist (phenylephrine, 50 µL, 1 mmol/L), and 4) α1-adrenergic receptor antagonist prazosin (30 µL, 1 mmol/L) or tamsulosin (50 µL, 1 mmol/l). ES of the SCG enhanced CB-evoked sympathoexcitation by 40-50% (P < 0.05) with no difference between rat strains. Unilateral SCGx attenuated the CB-evoked sympathoexcitation in SH (62%; P < 0.01) but was without effect in Wistar rats; it also abolished the ongoing firing of chemoreceptive petrosal neurones of SH rats, which became hyperpolarized. In Wistar rats, CB injections of phenylephrine enhanced CB-evoked sympathoexcitation (33%; P < 0.05), which was prevented by prazosin (26%; P < 0.05) in SH rats. Tamsulosin alone reproduced the effects of prazosin in SH rats and prevented the sensitizing effect of the SCG following ES. Within the CB, α1A- and α1B-adrenoreceptors were co-localized on both glomus cells and blood vessels. In conscious SH rats instrumented for recording blood pressure, the CB-evoked pressor response was attenuated after SCGx, and systolic BP fell by 16 ± 4.85 mmHg. Conclusions The sympathetic innervation of the CB is tonically activated and sensitizes the CB of SH but not Wistar rats. Furthermore, sensitization of CB-evoked reflex sympathoexcitation appears to be mediated by α1-adrenoceptors located either on the vasculature and/or glomus cells. The SCG is novel target for controlling CB pathophysiology in hypertension. Translational perspective Severing the main connection between the SCG and CB (i.e., the ganglioglomerular nerve) is a potential translational approach for normalizing CB sensitivity and as a treatment for hypertension. Selective denervation of the ganglioglomerular nerve in humans would mean that both the CB and SCG maintain their physiological function thereby minimizing any side-effects.

Contribution of the carotid body to thermally mediated hyperventilation in humans

“…Increased carotid body tonic activity with heating could potentially be explained by: (1) a direct effect of temperature on the carotid body's metabolic rate via the Q 10 effect (Baron & Eyzaguirre, 1977; Eyzaguirre et al., 1983; McQueen & Eyzaguirre, 1974); (2) increased efferent sympathetic nerve activity to the carotid body, which has been shown to increase both its tonicity and sensitivity in reduced preparations (Eyzaguirre et al., 1961; Felippe et al., 2022; Gagnon et al., 2015); or (3) via an increase in systemic $${\dot{V}}_{{\rm{CO}}_{\rm{2}}}$$, which has been linked to carotid body activation (Forster et al., 2012; Stickland et al., 2008; Weil et al., 1972).…”

Time-dependent alteration in the chemoreflex post-acute lung injury

“…The post ganglionic axons of the SCG are known to innervate the CBs ( Iturriaga et al, 2016 ). Electrical stimulation of the SCG has been shown to significantly sensitize the CB chemoreflex in hypertensive and normotensive rats ( Felippe and Paton, 2021 ; Getsy et al, 2021 ; Felippe et al, 2022 ). Therefore, an increased SCG neuronal activity during the recovery of ALI, in-part, might also contribute to chemoreflex sensitization observed in our study.…”

A Methodological Perspective on the Function and Assessment of Peripheral Chemoreceptors in Heart Failure: A Review of Data from Clinical Trials

“…As we mentioned above, CBs not only modulate sympathetic activation but also receive innervation from both sympathetic and parasympathetic systems. Animal studies revealed that the efferent impulsation in these nerves, specifically sympathetic stimulation, influences PChS [ 62 , 63 ], which could be caused by direct stimulation or vasoconstriction causing the hypoperfusion of CBs.…”