Hypertension – a visceral afferent problem

      In most cases essential hypertension involves a neurogenic component. Conventionally, neurogenic hypertension is defined as an over active sympathetic nervous system leading to elevated total peripheral resistance and/or raised cardiac output. However, in addition to raised sympathetic motor outflow, I would like to propose that the term neurogenic hypertension also refers to scenarios of pathogenic afferent signalling. One organ we study is the carotid body that via its reflex pathways provides a powerful excitatory stimulus to neuronal networks driving sympathetic activity. I will describe that in conditions of hypertension the carotid body develops aberrant tonic afferent drive. This pathological activity provides a major drive to chronically raise sympathetic motor activity. Removal of the carotid body in animals or its resection in humans lowers arterial pressure. This procedure appears effective in different types of hypertension (genetic versus renal) and species (rats, sheep, human) and involves reductions in sympathetic activity and improvement in renal function. I will describe that a major contributor to the aberrant activity of carotid body signalling is via ATP acting on P2X3 receptors and that their specific blockade abolishes carotid body aberrant discharge in hypertension, normalises reflex sensitivity (but, importantly, preserves physiological reflex function), and causes a substantial dose-dependent reduction in arterial pressure. I conclude that P2X3 receptor antagonism may provide a novel anti-hypertensive strategy in patients with hypertension.
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