Noradrenaline spillover and microneurography measurements in patients with primary hypertension

Quantification of sympathetic nervous activity is important in hypertension as the sympathetic system may play both long-term and short-term roles in cardiovascular regulation; it may be involved in the initiation of hypertension, the complications of hypertension, and anti-adrenergic drugs also reduce mortality. Of the clinical tests available at present, microneurography and noradrenaline overflow are measures of different aspects of sympathetic activity. Other indirect measures including reflex testing, autonomic blockade, and power spectral analysis provide indices of sympathetically mediated responses. The latter are therefore influenced by variations in function not only of the sympathetic system but also the organ mediating the response under investigation. Plasma noradrenaline concentration measurements are confounded by the influence of noradrenaline plasma clearance on plasma concentration. Antecubital venous samples represent the venous drainage of the forearm and are not typical of other vascular beds. The inability to detect regional differentiation of sympathetic responses is a feature of all 'global' measures of sympathetic function. Microneurographic recordings of sympathetic nerve fibre firing rates provide direct and continuous measurements of efferent activity to the skin and muscle. Regional noradrenaline spillover measurements, performed with infusions of radiolabelled noradrenaline and sampling from centrally placed catheters, may be used clinically to study internal organs not accessible to nerve recording with microneurography. Primary hypertension is characterized by preferential activation of the cardiac, skeletal muscle and renal sympathetic outflow particularly in younger patients. Central nervous system overflow of noradrenaline is also increased, providing an attractive rationale for the investigation of new centrally acting antihypertensive drugs. Activation of forebrain pressor noradrenergic nuclei may be an underlying mechanism for sympathetic activation in a proportion of patients with primary hypertension.