The sympathetic nervous system exacerbates carotid body sensitivity in hypertension

Author(s)

Felippe, Igor S. A. ; Zera, Tymoteusz ; da Silva, Melina P. ; Moraes, Davi J. A. ; McBryde, Fiona ; Paton, Julian F. R.

• Document type: Journal article
• Source: Cardiovascular Research; v. N/A, p. 16-pg., 2022-01-20.

Abstract

Aims The carotid bodies (CBs) 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 mu L, 0.4 mu g/mu L) in SH and Wistar rats in situ before and after: (i) electrical stimulation (ES; 30 Hz, 2 ms, 10 V) of the superior cervical ganglion (SCG), which innervates the CB; (ii) unilateral resection of the SCG (SCGx); (iii) CB injections of an alpha 1-adrenergic receptor agonist (phenylephrine, 50 mu L, 1 mmol/L), and (iv) alpha 1-adrenergic receptor antagonist prazosin (40 mu L, 1 mmol/L) or tamsulosin (50 mu L, 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, alpha 1A- and alpha 1B-adrenoreceptors were co-localized on both glomus cells and blood vessels. In conscious SH rats instrumented for recording blood pressure (BP), 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 alpha(1)-adrenoceptors located either on the vasculature and/or glomus cells. The SCG is novel target for controlling CB pathophysiology in hypertension. [GRAPHICS] . (AU)

• FAPESP's process: 19/11863-6 - Synaptic transmission and electrophysiological properties of bronchial motoneurons of the dorsal motor nucleus of the vagus from rats
• Grantee: Davi José de Almeida Moraes
• Support Opportunities: Regular Research Grants