Sympathomodulatory Effects of Antihypertensive Drug Treatment

BACKGROUND: An activation of sympathetic neural influences to the heart and peripheral circulation has been shown to represent a hallmark of the essential hypertensive state, adrenergic neural factors participating together with other variables at the development and progression of the high blood pressure state as well as of the hypertension-related target organ damage. This represents the rationale for employing in hypertension treatment drugs which combine the blood pressure-lowering properties with the modulatory effects on the sympathetic neural function. METHODS AND RESULTS: Several studies published during the past 40 years have investigated the impact of antihypertensive drugs on the sympathetic target as assessed by indirect and direct approaches. In the present paper, the effects of different monotherapies or combination drug treatment used in hypertension to lower elevated blood pressure values on various adrenergic markers will be examined. This will be followed by a discussion of the (i) hemodynamic and nonhemodynamic consequences of employing antihypertensive drugs with sympathomodulatory or sympathoexcitatory properties and (ii) mechanisms potentially responsible for the adrenergic responses to a given antihypertensive drug. The final part of this review will address the questions still open related to the impact of antihypertensive drug treatment on sympathetic function. Two questions in particular will be examined, i.e., whether antihypertensive drugs with sympathomodulatory properties may be capable to fully restore a "normal" adrenergic drive and how far sympathetic activity should be reduced in hypertensive patients. CONCLUSION: Future investigations aimed at answering these questions will be needed in order to improve cardiovascular protection in treated hypertensive patients.