Abstract P180: Blood Pressure Lowering During Chronic Baroreflex Activation: Don’t Forget the Heart

Abstract

Electrical stimulation of the baroreflex chronically suppresses sympathetic activity and arterial pressure (AP) and is currently being evaluated for the treatment of resistant hypertension. The antihypertensive effects of baroreflex activation (BA) are often attributed to renal sympathoinhibition. However, BA also decreases heart rate (HR) and, surprisingly, robust blood pressure lowering occurs even after renal denervation. Accordingly, responses to BA were simulated under normal conditions and after blockade of changes in renal sympathetic nerve activity (fixed RSNA) and autonomic activity to the heart (fixed HR) using an established mathematical model of human physiology (HumMod). Three week responses to BA closely mimicked our actual experimental observations in dogs including a 40% decrease in plasma [norepinephrine] (and RSNA in the simulation). With RSNA and HR fixed at control levels, mean AP (MAP), HR, right atrial pressure (RAP) and plasma atrial natriuretic peptide (ANP) responses to BA were: Changes in autonomic activity to the heart during BA lead to bradycardia, increases in atrial pressure and ANP secretion. Increased ANP and suppression of RSNA enhance renal excretory function and normally account for most of the hypotensive response to BA. However, when suppression of RSNA is not possible, blood pressure lowering in response to BA is not appreciably impaired due to inordinate fluid accumulation and further increases in atrial pressure and ANP secretion. These simulations provide a mechanistic understanding of experimental and clinical observations showing that BA effectively lowers blood pressure in subjects with previous renal denervation.