β-Adrenoceptor blockade prevents carotid body hyperactivity and elevated vascular sympathetic nerve density induced by chronic intermittent hypoxia.

Abstract

Carotid body (CB) hyperactivity promotes hypertension in response to chronic intermittent hypoxia (CIH). The plasma concentration of adrenaline is reported to be elevated in CIH and our previous work suggests that adrenaline directly activates the CB. However, a role for chronic adrenergic stimulation in mediating CB hyperactivity is currently unknown. This study evaluated whether beta-blocker treatment with propranolol (Prop) prevented the development of CB hyperactivity, vascular sympathetic nerve growth and hypertension caused by CIH. Adult male Wistar rats were assigned into 1 of 4 groups: Control (N), N + Prop, CIH and CIH + Prop. The CIH paradigm consisted of 8 cycles h-1, 8 h day-1, for 3 weeks. Propranolol was administered via drinking water to achieve a dose of 40 mg kg-1 day-1. Immunohistochemistry revealed the presence of both β1 and β2-adrenoceptor subtypes on the CB type I cell. CIH caused a 2-3-fold elevation in basal CB single-fibre chemoafferent activity and this was prevented by chronic propranolol treatment. Chemoafferent responses to hypoxia and mitochondrial inhibitors were attenuated by propranolol, an effect that was greater in CIH animals. Propranolol decreased respiratory frequency in normoxia and hypoxia in N and CIH. Propranolol also abolished the CIH mediated increase in vascular sympathetic nerve density. Arterial blood pressure was reduced in propranolol groups during hypoxia. Propranolol exaggerated the fall in blood pressure in most (6/7) CIH animals during hypoxia, suggestive of reduced sympathetic tone. These findings therefore identify new roles for β-adrenergic stimulation in evoking CB hyperactivity, sympathetic vascular hyperinnervation and altered blood pressure control in response to CIH.

• Authors: Abdulaziz A Alzahrani, Lily L Cao, Hayyaf S Aldossary, Demitris Nathanael, Jiarong Fu, Clare J Ray, Keith L Brain, Prem Kumar, Andrew M Coney, Andrew P Holmes
• Journal: Pflugers Archiv : European journal of physiology (Pflugers Arch) Vol. 473 Issue 1 Pg. 37-51 (01 2021) ISSN: 1432-2013 [Electronic] Germany
• PMID: 33210151 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adrenergic beta-Antagonists
• Receptors, Adrenergic, beta-1
• Receptors, Adrenergic, beta-2
• Carbon Dioxide
• Propranolol

Topics

• Adrenergic beta-Antagonists
• Animals
• Blood Pressure (drug effects)
• Carbon Dioxide
• Carotid Body (drug effects)
• Drug Administration Schedule
• Hypoxia
• Male
• Propranolol (pharmacology)
• Rats
• Rats, Wistar
• Receptors, Adrenergic, beta-1 (genetics, metabolism)
• Receptors, Adrenergic, beta-2 (genetics, metabolism)
• Sympathetic Nervous System (drug effects)