Journal article
Cardiovascular Regulation by the Neuronal BBSome
Hypertension (Dallas, Tex. 1979), Vol.75(4), pp.1082-1090
04/2020
DOI: 10.1161/HYPERTENSIONAHA.119.14373
PMID: 32148123
Abstract
The BBSome, a complex of eight Bardet-Biedl syndrome (BBS) proteins known for its role in the control of cilia function and other cellular processes, has been implicated in blood pressure control, but the underlying mechanisms are not fully understood. Here, we show that neuronal BBSome plays an important role in blood pressure regulation. Targeted inactivation of the BBSome in the nervous system through
Bbs1
gene deletion causes sympathetically-mediated increase in blood pressure in mice. This phenotype is reproduced by selective ablation of the
Bbs1
gene from the leptin receptor (LRb)-expressing neurons. Strikingly, the well-known role of the BBSome in the regulation of cilia formation and function is unlikely to account for the prohypertensive effect of BBSome inactivation as disruption of the intraflagellar transport (IFT) machinery required for ciliogenesis by deleting the
Ift88
gene in LRb neurons had no effect on arterial pressure and sympathetic nerve activity. Furthermore, we found that
Bbs1
gene deletion from agouti-related protein (AgRP) neurons or proopiomelanocortin (POMC) neurons increased renal and splanchnic sympathetic nerve activity without altering blood pressure. This lack of blood pressure increase despite the sympathetic overdrive may be explained by vascular adrenergic desensitization as indicated by the reduced vascular contractile response evoked by phenylephrine and the decreased expression of adrenergic receptors. Our results identify the neuronal BBSome as a new player in hemodynamic, sympathetic and vascular regulation, in a manner independent of cilia.
Details
- Title: Subtitle
- Cardiovascular Regulation by the Neuronal BBSome
- Creators
- Deng-Fu Guo - Department of Neuroscience and Pharmacology, University of Iowa Carver College of Medicine, Iowa City, IowaJohn J Reho - Department of Neuroscience and Pharmacology, University of Iowa Carver College of Medicine, Iowa City, IowaDonald A Morgan - Department of Neuroscience and Pharmacology, University of Iowa Carver College of Medicine, Iowa City, IowaKamal Rahmouni - Department of Neuroscience and Pharmacology, University of Iowa Carver College of Medicine, Iowa City, Iowa
- Resource Type
- Journal article
- Publication Details
- Hypertension (Dallas, Tex. 1979), Vol.75(4), pp.1082-1090
- DOI
- 10.1161/HYPERTENSIONAHA.119.14373
- PMID
- 32148123
- NLM abbreviation
- Hypertension
- ISSN
- 0194-911X
- eISSN
- 1524-4563
- Language
- English
- Date published
- 04/2020
- Academic Unit
- Iowa Neuroscience Institute; Fraternal Order of Eagles Diabetes Research Center; Neuroscience and Pharmacology; Internal Medicine
- Record Identifier
- 9984070867502771
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