Positive chronotropic and inotropic responses to release of norepinephrine from sympathetic nerve terminals produced by nitroglycerin in atria.
Nitroglycerin produced concentration-dependent increases in spontaneous rate and enhancements of positive chronotropic and inotropic responses to transmural stimulation of isolated right guinea-pig atria. The effects of nitroglycerin were significantly potentiated by desmethylimipramine, which is an inhibitor of norepinephrine uptake, and were significantly inhibited by either guanethidine, which inhibits release of norepinephrine, or alpha-methyl-p-tyrosine, which inhibits synthesis of norepinephrine. The effects of nitroglycerin were not modified by either prazosin or atropine, but were significantly inhibited by either the beta-adrenoceptor antagonist propranolol or the alpha 2-adrenoceptor antagonist yohimbine. Nitroglycerin significantly increased the concentration of norepinephrine in the medium bathing atria and the 3,4-dihydroxyphenylglycol concentration in the atrial tissue, which were quantified using high-performance liquid chromatography with electrochemical detection. The atrial responses to nitroglycerin appear to mimic sympathetic neuronal activities and may involve the modulatory role of alpha 2-adrenoceptors in the release of norepinephrine.
Ma
S X
SX
Department of Pharmacology, College of Medicine, University of Iowa, Iowa City 52242.
Long
J P
JP
D000818:Animals; D006168:Guinea Pigs; D006321:Heart / Q000294:innervation; D006325:Heart Atria / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects*; D066298:In Vitro Techniques; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives / Q000378:metabolism; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism; D009411:Nerve Endings / Q000187:drug effects / Q000378:metabolism*; D005996:Nitroglycerin / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism*; D013268:Stimulation, Chemical; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000378:metabolism*
D008734:Methoxyhydroxyphenylglycol; D005996:Nitroglycerin; C010117:3,4-dihydroxyphenylglycol; D009638:Norepinephrine