Noradrenergic mechanisms and the cardiovascular actions of nitroglycerin.
In this article we review noradrenergic activities of nitroglycerin in the central and peripheral nervous systems. Nitroglycerin may cause paradoxical bradycardia and occasional life threatening hypotension in patients. Intracisternal injections and microinjections of nitroglycerin into nucleus tractus solitarii produce hypotension and bradycardia, effects which mimic the baroreflex and may involve central noradrenergic mechanisms. The drug also triggers an alpha 2-adrenoceptor-mediated sympatho-inhibition reflex through vagal afferents. Nitroglycerin mimics biological responses associated with sympathetic neuronal activity, e.g., increase in outflow of norepinephrine and its metabolites from perfused guinea pig atria, medulla-pons tissue and cerebrospinal fluid. The sympathomimetic effects of nitroglycerin are antagonized by pre-treatment with yohimbine or rauwolscine. Clinical studies and animal experiments show that hemodynamics of nitroglycerin and sodium nitroprusside are different. Nitroglycerin is lipophilic and the compounds readily enters cells to form nitric oxide, but sodium nitroprusside is very hydrophilic and the compound has difficulty crossing membranes. Thus, intravenous nitroglycerin-induced increases in central noradrenergic activation and inhibitory reflexes may account for at least some of the therapeutic actions and side effects of the drug. In contrast, minimal central responses are produced by intravenous administration of sodium nitroprusside.
Department of Internal Medicine, University of Iowa College of Medicine, Iowa City.
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D000818:Animals; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007022:Hypotension / Q000139:chemically induced; D009200:Myocardial Contraction / Q000187:drug effects; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology; D005996:Nitroglycerin / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism*; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects; D013564:Sympathetic Nervous System / Q000187:drug effects*; D014630:Vagus Nerve / Q000187:drug effects / Q000502:physiology
D011942:Receptors, Adrenergic, alpha; D005996:Nitroglycerin; D009638:Norepinephrine