Regional sympathetic function in renovascular hypertension

Abstract

In renovascular hypertension (RVH) the renin-angiotensin system is of major importance for the early development of hypertension, whereas its role during the chronic phase has been disputed. There are several lines of evidence to suggest elevated sympathetic nerve activity to maintain the blood pressure increase during the chronic phase of RVH. The current study was undertaken to explore regional sympathetic nerve activity in relation to the activity of the renin-angiotensin system and to the long-term survival in RVH, to assess cardiorenal epinephrine (EPI) kinetics and to evaluate two non-invasive procedures for diagnosing RVH.Isotope dilution with measurement of overall and regional norepinephrine (NE) and EPI spillover was used to estimate overall and regional sympathetic nerve activity and EPI kinetics in patients with renal artery stenosis, patients with congestive heart failure and healthy subjects. In subgroups, efferent muscle sympathetic nerve activity (MSA) was recorded by microneurography. Long-term survival was assessed in consecutive hypertensive patients with renovascular disease in relation to plasma NE concentration. Duplex ultrasound, captopril renography and renal angiography were performed in consecutive hypertensive patients referred for evaluation of RVH.Both total body NE spillover and MSA were elevated in RVH patients compared to healthy subjects. Cardiovascular mortality in hypertensive patients with renovascular disease was high but there was no association between to the plasma NE concentrations. Acute administration of enalaprilat, an angiotensin converteing enzyme (ACE) inhibitor to hypertensive patients with renovascular disease provoked a differentiated sympathetic nerve response with unchanged total body NE spillover, MSA and heart rate, whereas renal NE spillover increased. Patients with cardiovascular diseases showed a small but consistent cardiorenal EPI spillover at baseline. Cardiac EPI spillover increased during exercise, whereas renal EPI spillover could not be detected. Both duplex ultrasound and captopril renography showed high specificity and negative predictive values for detection of renal artery stenosis, whereas sensitivity appeared higher for duplex ultrasound.This study establishes elevated sympathetic nerve activity in RVH, consistent with increased central sympathetic outflow. Blood pressure reduction following acute ACE inibition in hypertensive patients with renovascular disease provoked differentiated sympathetic response, inasmuch that overall and muscle sympathetic reflex activation were blunted, whereas the reflex renal sympathetic response to blood pressure reduction was preserved. These effects on sympathetic nerve activity by ACE inhibition are consistent with a central site of action. Epinephrine released from cardiac sympathetic neurons may facilitate NE release by stimulation of pre-synaptic ?2 receptors. This mechanism could be of importance for the adrenergic overactivity associated with different cardiovascular diseases. Given that duplex ultrasound is at least as accurate as captopril renography for detection of renal artery stenosis and easier to perform, we consider it first choice method when screening for RVH.