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.

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(2017). Carotid body resection for sympathetic modulation in systolic heart failure -results from first-in-man study. ABSTRACT AimsAugmented reflex responses from peripheral chemoreceptors, which are mainly localized in the carotid bodies (CB), characterize patients with systolic heart failure (HF) and contribute to adrenergic hyperactivation. We investigated whether surgical resection of CB in these patients can be performed safely to decrease sympathetic tone. Methods and resultsWe studied 10 male patients with systolic HF (age: 59±3 years, left ventricular ejection fraction: 27±7%) who underwent unilateral right-sided CB resection (4 patients) or bilateral CB resection (6 patients).Primary endpoints of the study were changes in muscle sympathetic nerve activity (MSNA) and peripheral chemosensitivity measured as ventilatory response to hypoxia from baseline to 1 month post-CB resection. Safety analysis included analysis of arterial blood gas and oxygenation at night through 2 months post-procedure and adverse events assessed up to 12-months.At 1-month visit, CB resection was associated with a significant decrease in both MSNA (86.6±3.1 vs.79.7±4.2 bursts/100 beats, p=0.03) and in peripheral chemosensitivity (1.35±0.19 vs. 0.41±0.17 L/min/SpO2, p=0.005). It also resulted in improved exercise tolerance. Amongst some patients with bilateral CB resection there was a trend towards worsening of oxygen saturation at night, which in one case required therapy with non-invasive ventilation. ConclusionWe present first-in-man evidence that CB resection in patients with systolic HF is associated with decrease in sympathetic activity. Bilateral procedure may carry a risk of worsening oxygenation at night.CB modulation constitutes an interesting research avenue, but careful consideration of the balance between safety and efficacy is necessary before further clinical trials.