Targeting the carotid body as a therapeutic strategy for controlling sympathetically mediated diseases

      The carotid body chemoreceptor is said to be the most perfused tissue per unit weight in the body. In the rabbit this is 1203 ± 126 ml min−1 100 g−1[1], which is similar to that reported in the cat [2]. It responds to hypoxia, pH, and hypercapnia evoking increases in breathing and a pattern of cardiovascular response that depend on the degree of lung inflation. Its physiological roles likely include initiation of breathing at birth, breathing stability throughout life and blood pH regulation. It is now clear that the carotid body chemoreceptor plays a role in disease states characterized by excess sympathetic nervous activity. In animal models, the hypertension associated with chronic intermittent hypoxia depends entirely on the carotid body[3]. An augmented hypoxic ventilatory response is a strong predictor of morbidity in patients with heart failure [4]. Both animal models and humans with heart failure or hypertension have increased peripheral chemoreceptor reflex gain as portrayed by an elevated hypoxic ventilatory response [4,5]. In my presentation, I will make the case that in conditions of an overactive sympathetic nervous system, such as neurogenic hypertension, the carotid body acquires tonicity that contributes, in part, to the high blood pressure and sympathetic over-activity, and to a depression of baroreceptor reflex gain as well as being pro-inflammatory. I will shed light on the idea that carotid body glomus cells have reflex functional (i.e. end organ) specificity and explore the notion that reducing afferent drive from the carotid body may be therapeutically beneficial in animal models of hypertension and human hypertensive patients that are drug resistant or intolerant.
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