Chronic Interactions Between Carotid Baroreceptors and Chemoreceptors in Obesity Hypertension

Abstract

Carotid bodies play a critical role in protecting against hypoxemia and their activation increases sympathetic activity, arterial pressure and ventilation, responses opposed by acute stimulation of the baroreflex. While chemoreceptor hypersensitivity is associated with sympathetically-mediated hypertension, the mechanisms involved and their significance in the pathogenesis of hypertension remains unclear. We investigated the chronic interactions of these reflexes in dogs with sympathetically-mediated, obesity-induced hypertension based on the hypothesis that hypoxemia and tonic activation of carotid chemoreceptors may be associated with obesity. After 5 weeks on a high-fat diet, the animals experienced a 35–40% weight gain, increases in arterial pressure from 106±3 to 123±3 mm Hg and respiratory rate from 8±1 to 12±1 breaths/min along with hypoxemia (PaO2= 81±3 mm Hg) but eucapnia. During 7 days of carotid baroreflex activation by electrical stimulation of the carotid sinus, tachypnea was attenuated and hypertension was abolished before these variables returned to pre-stimulation values during a recovery period. Following subsequent denervation of the carotid sinus region, respiratory rate decreased transiently in association with further sustained reductions in PaO2 (to 65±2 mm Hg) and substantial hypercapnia. Moreover, the severity of hypertension was attenuated from 125±2 to 116±3 mm Hg (45–50% reduction). These findings suggest that hypoxemia may account for sustained stimulation of peripheral chemoreceptors in obesity and that this activation leads to compensatory increases in ventilation and central sympathetic outflow that contributes to neurogenically-mediated hypertension. Furthermore, the excitatory effects of chemoreceptor hyperactivity are abolished by chronic activation of the carotid baroreflex.

Sympathetic activity in obesity: a brief review of methods and supportive data

“…84 Carotid baroreflex activation has been shown to reduce blood pressure, heart rate, and plasma norepinephrine in this model. 84,85 A blunted sympathetic baroreflex has been observed in both clinical and experimental obesity, 86,87 and weight loss is associated with an improvement in sympathetic baroreflex function. 55 Grassi and colleagues have further demonstrated that the association between obesity and hypertension is associated with impairment in both sympathetic and vagal baroreflex cardiovascular control and that the magnitude of impairment is greater in those with combined obesity-related hypertension than in those with either obesity or hypertension alone.…”

Prolonged Baroreflex Activation Abolishes Salt-Induced Hypertension After Reductions in Kidney Mass

“…49 However, this has not been our experience when using the Barostim Neo system during chronic bilateral carotid sinus activation in canines. 33,50 Randomized controlled trials are needed to thoroughly evaluate whether the Barostim Neo electrode system may have clinical utility in managing RHT.…”

Atrial Fibrillation and Hypertension

“…Obesity is strongly linked to cardiometabolic comorbidities including hypertension, diabetes mellitus, and obstructive sleep apnea. 79,80 Similarly, increasing body mass index is related to increased risk of AF. 2 Interventions to reduce body weight have numerous positive health effects in AF patients, including BP reduction, decrease in glucose, total cholesterol, low-density cholesterol, and triglycerides, inhibition of inflammation (eg, reduction in C-reactive protein levels), attenuation of pathological LA remodeling (ie, decrease in LA volume) and LV remodeling (reduction of LV hypertrophy and E/eʹ ratio).…”