Arterial chemoreceptors and sympathetic nerve activity: Implications for hypertension and heart failure

Chemoreceptor input is exaggerated in CHF and hypertension by chemical and hemodynamic factors in the CB. As we have summarized here, a predisposing factor involved in the enhanced chemoreceptor activity appears to be oxidative stress because of impaired oxygen delivery to the CB, either by way of intermittent hypoxic exposure from periodic apneas or reduced blood flow from impaired cardiac or vascular function (Figure 4). In CHF, upregulation of Ang II/NADPH oxidase and downregulation of NOS in the CB secondary to reduced blood flow contribute to this effect. In SA-related hypertension, upregulation of 5-hydroxytryptamine/NADPH oxidase and downregulation of mitochondrial complex I in the CB secondary to periodic bouts of hypoxemia contribute to the effect. In essential hypertension, mechanisms for enhanced CB function remain unexplored but may be related to altered vascular function in the CB. Regardless of the initial stimulus, the resultant chronic activation of sympathetic outflow is likely to amplify and perpetuate the CB disturbance, in a feed-forward manner, by exacerbating deterioration of cardiac function and cardiac output with reduced flow to the CB in CHF and by vasoconstriction with reduced flow to the CB in hypertension. Future inroads in this area will rely on further identification of chemical stimuli, signaling pathways, altered gene expression, and transcription factors responsible for this cascade of events on neural and vascular function within the CB.