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.

Key points• Peripheral chemoreflex sensitivity is enhanced in hypertension yet the role of these receptors in the development and maintenance of high blood pressure remains unknown.• Carotid chemoreceptors were denervated in both young and adult spontaneously hypertensive rats (SHRs) by sectioning the carotid sinus nerves bilaterally while recording arterial blood pressure chronically using radio telemetry.• Carotid sinus denervation (CSD) in the young animals prevented arterial pressure from reaching the hypertensive levels observed in sham-operated animals whereas in adult SHRs arterial pressure fell by ∼20 mmHg.• After CSD there was a decrease in sympathetic activity, measured indirectly using power spectral analysis and hexamethonium, and an improvement in baroreceptor reflex gain.• Carotid bodies are active in the SHR and contribute to both the development and maintenance of hypertension; whether carotid body ablation is a useful anti-hypertensive intervention in drug-resistant hypertensive patients remains to be resolved. AbstractThe peripheral chemoreflex is known to be enhanced in individuals with hypertension. In pre-hypertensive (PH) and adult spontaneously hypertensive rats (SHRs) carotid body type I (glomus) cells exhibit hypersensitivity to chemosensory stimuli and elevated sympathoexcitatory responses to peripheral chemoreceptor stimulation. Herein, we eliminated carotid body inputs in both PH-SHRs and SHRs to test the hypothesis that heightened peripheral chemoreceptor activity contributes to both the development and maintenance of hypertension. The carotid sinus nerves were surgically denervated under general anaesthesia in 4-and 12-week-old SHRs. Control groups comprised sham-operated SHRs and aged-matched sham-operated and carotid sinus nerve denervated Wistar rats. Arterial blood pressure was recorded chronically in conscious, freely moving animals. Successful carotid sinus nerve denervation (CSD) was confirmed by testing respiratory responses to hypoxia (10% O 2 ) or cardiovascular responses to I.V. injection of sodium cyanide. In the SHR, CSD reduced both the development of hypertension and its maintenance (P < 0.05) and was associated with a reduction in sympathetic vasomotor tone (as revealed by frequency domain analysis and reduced arterial pressure responses to administration of hexamethonium; P < 0.05 vs. sham-operated SHR) and an improvement in baroreflex sensitivity. No effect on blood pressure was observed in sham-operated SHRs or Wistar rats. In conclusion, carotid sinus nerve inputs from the carotid body are, in part, responsible for elevated sympathetic tone and critical for the genesis of hypertension in the developing SHR and its maintenance in later life.

No abstract