The carotid body as a putative therapeutic target for the treatment of neurogenic hypertension

• Published in: Nature communications 2013-09, Vol.4 (1), p.2395-2395, Article 2395
• Main Authors: McBryde, Fiona D., Abdala, Ana P., Hendy, Emma B., Pijacka, Wioletta, Marvar, Paul, Moraes, Davi J. A., Sobotka, Paul A., Paton, Julian F. R.
• Format: Article
• Language: English
• Subjects: 631/443/1338/243/785; 631/443/376; 692/308; Animals; Arterial Pressure - physiology; Baroreflex - physiology; Blood pressure; Carotid Body - metabolism; Carotid Body - surgery; Carotid Sinus - innervation; Carotid Sinus - surgery; Cell Movement - immunology; Denervation; Drug resistance; Heart - physiology; Humanities and Social Sciences; Hyperoxia; Hypertension; Hypertension - metabolism; Hypertension - therapy; Kidney - innervation; Kidney - surgery; Male; multidisciplinary; Physiology; Rats; Rats, Inbred SHR; Rats, Wistar; Science; Science (multidisciplinary); Sympathetic Nervous System - metabolism; Sympathetic Nervous System - surgery; T-Lymphocytes - immunology; Variance analysis
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms3395

In the spontaneously hypertensive (SH) rat, hyperoxic inactivation of the carotid body (CB) produces a rapid and pronounced fall in both arterial pressure and renal sympathetic nerve activity (RSA). Here we show that CB de-afferentation through carotid sinus nerve denervation (CSD) reduces the overactive sympathetic activity in SH rats, providing an effective antihypertensive treatment. We demonstrate that CSD lowers RSA chronically and that this is accompanied by a depressor response in SH but not normotensive rats. The drop in blood pressure is not dependent on renal nerve integrity but mechanistically accompanied by a resetting of the RSA–baroreflex function curve, sensitization of the cardiac baroreflex, changes in renal excretory function and reduced T-lymphocyte infiltration. We further show that combined with renal denervation, CSD remains effective, producing a summative response indicative of an independent mechanism. Our findings indicate that CB de-afferentation is an effective means for robust and sustained sympathoinhibition, which could translate to patients with neurogenic hypertension. Enhanced sympathetic drive from chemoreceptors in the carotid body contributes to hypertension. Here McBryde et al . show that carotid sinus denervation is an effective antihypertensive treatment in rats with neurogenic hypertension even if performed in addition to renal denervation.