The sympathetic nervous system in renovascular hypertension: lead actor or ‘bit’ player? Guido Grassi a and Murray Esler b Journal of Hypertension 2002, 20:1071–1073 a Clinica Medica, Dipartimento di Medicina Clinica, Prevenzione e Biotecnologie Sanitarie, Universita ` Milano Bicocca, Centro Interuniversitario di Fisiologia Clinica e Ipertensione, Istituto Auxologico Italiano, Milan, Italy and b Baker Medical Research Institute, Prahran 3181, Melbourne, Victoria, Australia. Correspondence and requests for reprints to Professor Guido Grassi, Clinica Medica, Ospedale S. Gerardo dei Tintori, Via Donizetti 106, 20052 Monza, Milan, Italy. Tel: +39 0233 3357; fax: +39 0322 274; e-mail: guido.grassi@unimib.it During recent years, several issues concerning the role of the sympathetic nervous system in the pathophysiol- ogy of the hypertensive state have been thoroughly investigated and successfully clarified. An updated picture of the information collected to date on this topic can be summarized as follows. First, in most published reports, essential hypertension is almost invariably characterized by an activation of the sympa- thetic nervous system, as confirmed by the increased circulating noradrenaline, muscle sympathetic nerve traffic and systemic noradrenaline spillover values reported by different investigators in essential hyper- tensive patients [1–5]. Second, this adrenergic acti- vation contributes to the development, as well as to the progression, of the hypertensive disorder, directly parti- cipating not only in the blood pressure elevation, but also in the pathogenesis of the target organ damage characterizing the disease [6,7]. Third, the hyper- tension-related increase in adrenergic cardiovascular drive is widespread, involving several circulatory dis- tricts, including the cerebral, renal, cardiac and muscu- lar ones, with the only exception being represented by the cutaneous circulation in which sympathetic nerve traffic has been reported to be within the normal range (Table 1) [8,9]. Fourth, the adrenergic overdrive ap- pears to be particularly pronounced in young and middle-aged patients, although recent findings also show its presence in systo-diastolic and isolated systolic hypertension of the elderly [10]. Finally, many mechan- isms appear to be responsible for the hypertension- related sympathoexcitation, including: (i) a dysfunction in the reflex influences (stemming from the arterial baroreceptors, the cardiopulmonary volume receptors and the chemoreceptors), which in physiological condi- tions tonically restrain central sympathetic outflow [11]; (ii) an ‘adrenergic reinforcement’ due to the excitatory effects exerted on sympathetic neural function, both at the central and peripheral level, by various humoral agents (such as angiotensin II, nitric oxide, endothelins, etc.) [11]; and (iii) an interaction between the sympa- thetic nervous system and metabolic variables (such as insulin) that have been documented to potentiate central sympathetic outflow [11]. More scarce and less univocal are the information on the behaviour of the sympathetic nervous system in secondary hypertension. The debate specifically con- cerns renovascular hypertension, given the agreement Table 1 Behaviour of regional sympathetic activity in different pathological conditions Sympathetic district Ess. HT Sec HT Obesity OB + HT CHF Liver cirrhosis Renal failure Cardiac : : # : : ? ? Renal : ? : : : ? ? Cerebral ? a ? ? ? ? ? ? Muscular : :# : :: : : : Cutaneous # ? # ? # # ? a In essential hypertension (Ess. HT), the increase in cerebral noradrenaline turnover is probably due to an increase in brain neuronal norepinephrine turnover rather than to a cerebral sympathetic activation. OB, Obesity; CHF, congestive heart failure; HT, hypertension; :, increase; #, decrease; ?, no information. Editorial comment 1071 0263-6352 & 2002 Lippincott Williams & Wilkins