Cardiovascular consequences of sympathetic hyperactivity.
The sympathetic nervous system plays an integral role in many aspects of cardiovascular homeostasis. However, intermittent or chronic sympathetic hyperactivity can also initiate or accelerate cardiovascular pathology and provoke clinical events in the presence of cardiovascular disease. Both alpha- and beta-receptors mediate these responses. In the case of the heart, alpha- and beta- receptors contribute to ventricular arrhythmias and cardiac hypertrophy. Moreover, cardiac beta2-receptors mediate not only chronotropic and inotropic responses at the postsynaptic level, but also noradrenalin release at the presynaptic level. To block the adverse effects of sympathetic hyperactivity optimally, one would therefore need both alpha- and nonselective beta-receptor blockade. On the other hand, prevention or reversal of sympathetic hyperactivity at the central level appears to be an attractive alternative. Alpha2-agonists such as clonidine and alpha-methyldopa are clearly effective in this regard but are associated with side effects. More recent research indicates that in the central nervous systen (CNS) other classes such as dihydropyridines (eg, nifedipine) or angiotensin II type 1 receptor blockers (eg, losartan) also can decrease elevated sympathetic nerve activity. The therapeutic relevance of these CNS effects and differences between lipophilic and hydrophilic compounds provide intriguing new avenues for research in disorders such as hypertension and congestive heart failure.
Leenen
F H
FH
Hypertension Unit, University of Ottawa Heart Institute, Ottawa, Canada. fleenen@ohi-net.heartinst.on.ca
D000818:Animals; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000378:metabolism; D002319:Cardiovascular System / Q000187:drug effects / Q000294:innervation* / Q000378:metabolism; D006439:Hemodynamics; D006801:Humans; D009206:Myocardium / Q000378:metabolism; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000378:metabolism*; D013565:Sympatholytics / Q000627:therapeutic use; D013566:Sympathomimetics / Q000627:therapeutic use
D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D013565:Sympatholytics; D013566:Sympathomimetics