The sympathetic system and hypertension*1

Measurement of regional sympathetic activity in lean essential hypertension patients using electrophysiologic (sympathetic nerve recording) and neurochemical (measurement of norepinephrine spillover) techniques demonstrates activation of sympathetic outflow to the heart, kidneys, and skeletal muscle vasculature in younger (< 45 years) patients. The increase in sympathetic activity is a mechanism for both initiating and sustaining the blood pressure elevation. Sympathetic nervous activation also confers specific cardiovascular risk. Stimulation of the sympathetic nerves to the heart promotes the development of left ventricular hypertrophy and contributes to the genesis of ventricular arrhythmias and sudden death. Sympathetically mediated vasoconstriction in skeletal muscle vascular beds reduces the uptake of glucose by muscle, and is thus a basis for insulin resistance and consequent hyperinsulinemia. Understanding the neural pathophysiology of obesity-related hypertension has been more difficult. In normotensive obesity, renal sympathetic tone is doubled, but cardiac norepinephrine spillover (a measure of sympathetic activity in the heart) is only 50% of normal. In obesity-related hypertension, there is a comparable elevation of renal norepinephrine spillover, but without suppression of cardiac sympathetics, as here cardiac norepinephrine spillover is more than double that of normotensive obese and 25% higher than in healthy volunteers. Increased renal sympathetic activity in obesity may be a necessary cause for the development of hypertension (predisposing to hypertension development), but apparently is not a sufficient cause. The discriminating feature of the obese who develop hypertension is the absence of the presumably adaptive suppression of cardiac sympathetic outflow seen in the normotensive obese. The sympathetic nervous system has moved towards center stage in cardiovascular medicine. The importance of sympathetic activation in heart failure progression and mortality and in the generation of ventricular arrhythmias is now well established. In essential hypertension also, although the mechanism differs somewhat between the lean and obese, the sympathetic nervous system is a key factor in the genesis of the disorder, and additionally promotes the development of complications. Through their central inhibition of sympathetic nervous activity, I1 agents such as rilmenidine powerfully reduce sympathetic nervous activity in essential hypertension patients, lowering blood pressure, and carrying the potential for specific cardiovascular protection.