Treating hypertension: when to say win.

What do we really know about sympathetic outflow and blood pressure in humans? For example, in healthy normotensive young subjects, baseline sympathetic outflow can vary 2-fold to 3-fold.1,2 We also know that in healthy aging subjects, baseline sympathetic outflow can be increased dramatically with only a modest impact on vascular resistance and little or no impact on blood pressure.1 Additionally, there is no clear evidence for dramatic increases in baseline sympathetic outflow in “garden variety” essential hypertension.1 If we stop here, a position of “nihilism” about sympathetic outflow and blood pressure seems reasonable. However, when the sympathetic nervous system is destroyed by disease or surgery, blood pressure is highly labile.3 We also know that many “stressors” that evoke a pressor response also evoke marked sympathetic activation, and that the magnitude of these pressor responses can be a harbinger of future hypertension.4,5 Finally, in disease states like congestive heart failure, excessive sympathetic activation is a “bad thing.”6,7 If we emphasize these points, sympathetic vasoconstriction seems more important to blood pressure and perhaps survival. In the middle of this confusion about sympathetic activity and blood pressure lie the baroreflexes that sense changes in arterial pressure and evoke increases in heart rate and sympathetic outflow when blood pressure is “low” and reciprocal responses when blood pressure is “high.” Together with their allies in the brain stem and kidney, they make the needed physiological adjustments so that in “normotension” there is an appropriate blood pressure for any given behavioral state. One mechanism that is essential to this flexible regulatory pattern is baroreflex “resetting.” During physiological conditions that require acute changes in blood pressure the baroreceptors quickly reset to do things like “defend” a higher arterial pressure during exercise or let pressure fall during sleep.8 However, in hypertension, chronic resetting of baroreflexes occurs so that a higher pressure is defended and the hypertensive state is maintained or even reinforced. If we are lucky, perhaps treatment of hypertension will reduce arterial pressure and reset the baroreflexes so that a more normal blood pressure is defended. In other words, we might get a 2-for-1 “physiological bargain” when hypertension is treated.