title: Effects of antihypertensive therapies on the sympathetic nervous system.
abstract: The sympathetic nervous system is a major modulator of cardiovascular function. Over the past three decades, numerous studies, using various methodologies, have reported the existence of a variety of pre- and postsynaptic sympathetic dysfunctions in essential hypertension. Most of these abnormalities facilitate sympathetic neurotransmission, resulting in a chronic increase in the sympathetic tone and reactivity in a significant proportion of hypertensive patients. Chronic sympathetic activation is also associated with major alterations in the balance among postsynaptic adrenergic receptors in cardiovascular tissues. Indeed, an attenuation of beta-adrenergic function and a potentiation of alpha1-adrenergic function has been demonstrated in cardiovascular tissues in hypertensive patients, suggesting the development of a sympathetic postsynaptic alpha1 dominance during the development and evolution of hypertension. Chronic activation of the sympathetic system is deleterious and could contribute to the development of most cardiovascular complications associated with hypertension. One of the major aims of antihypertensive therapy should thus be to attenuate pre- or postsynaptic sympathetic tone. Most antihypertensive drugs have been found to improve either pre- or postsynaptic sympathetic function in hypertensive patients. At the presynaptic level, diuretics were found to increase the liberation of noradrenalin, presumably through baroreflex sympathetic activation. In contrast, beta-blockers were shown to attenuate noradrenalin release from sympathetic nerves by blocking presynaptic facilitatory beta-receptors, thus reducing the sympathetic tone on postsynaptic receptors. Similarly, angiotensin-converting enzyme inhibitors or angiotensin II type 1 (AT1) receptor antagonists have been found to reduce sympathetic reactivity by acting on the central nervous system, but also by blocking AT1-mediated facilitatory mechanisms located on sympathetic fibres and in the adrenal medulla. Short acting dihydropyridine calcium channel blockers (CCBs) were found to enhance noradrenalin release from sympathetic nerves, but longer acting CCBs seems to have variable effects. Indeed, while the chronic slow release formulation of nifedipine gastrointestinal therapeutic system (GITS) did not raise circulating noradrenalin levels, treatment with amlodipine increased circulating noradrenalin levels, suggesting that nifedipine GITS is neutral on the sympathetic tone but that amlodipine chronically activates the sympathetic system. At the postsynaptic level, however, dihydropyridine CCBs were shown to attenuate the sympathetic tone on alpha1-adrenoceptors. In conclusion, it appears that most antihypertensive drugs interfere with pre- or postsynaptic sympathetic mechanisms and that these mechanisms could contribute to their hypotensive effects.
authors: Hôpital du Sacré-Coeur, Faculty of Medicine, Montréal, Canada. dechampj@physio.umontreal.ca
authors: J
authors: J
authors: de Champlain
authors: M
authors: M
authors: Karas
authors: C
authors: C
authors: Toal
authors: R
authors: R
authors: Nadeau
authors: P
authors: P
authors: Larochelle
mesh_terms: D018674:Adrenergic Antagonists / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D002121:Calcium Channel Blockers / Q000627:therapeutic use; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D009435:Synaptic Transmission / Q000187:drug effects
chemical_list: D018674:Adrenergic Antagonists; D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta