Effects of nitroglycerin on release, synthesis and metabolism of norepinephrine and activation of tyrosine hydroxylase in guinea-pigs.
Nitroglycerin produced concentration-dependent increases in outflow of norepinephrine (NE) in perfused guinea-pig hearts. These effects of nitroglycerin were inhibited by guanethidine, but were not blocked by desmethylimipramine or rauwolscine. Nitroglycerin-induced increases in NE outflow correlated with its positive chronotropic responses. Higher concentrations of nitroglycerin also increased outflow of 3,4-dihydroxyphenylglycol (DOPEG) which were inhibited by desmethylimipramine. Nitroglycerin-induced maximal outflow of NE occurred during the first 2 min, but maximal outflow of DOPEG was 2-4 min. In addition, the 3,4-dihydroxyphenylalanine formation in atrial and striatal slices were enhanced by nitroglycerin in the presence of m-hydroxybenzylhydrazine dihydrochloride (an inhibitor of aromatic L-amino acid decarboxylase). The results suggest that nitroglycerin increases release of NE which correlates with cardiac stimulation by the drug. The drug also stimulates tyrosine hydroxylase activity resulting in increased synthesis of NE.
Ma
S X
SX
Department of Pharmacology, College of Medicine, University of Iowa, Iowa City 52242.
Long
J P
JP
D000818:Animals; D001923:Brain Chemistry; D003342:Corpus Striatum / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D004295:Dihydroxyphenylalanine / Q000096:biosynthesis; D004789:Enzyme Activation; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives / Q000378:metabolism; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism; D005996:Nitroglycerin / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology*; D009638:Norepinephrine / Q000096:biosynthesis / Q000378:metabolism*; D010477:Perfusion; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism*
D008734:Methoxyhydroxyphenylglycol; D004295:Dihydroxyphenylalanine; D014446:Tyrosine 3-Monooxygenase; D005996:Nitroglycerin; C010117:3,4-dihydroxyphenylglycol; D009638:Norepinephrine