© 1995 American Heart Association, Inc.
Articles |
Endogenous and Exogenous Nitric Oxide Inhibits Norepinephrine Release From Rat Heart Sympathetic Nerves
From the Department of Pharmacology, Johannes Gutenberg University, Mainz, Germany (P.S., R.D., U.F.), and the Department of Anatomy and Neurobiology, Medical College of Ohio, Toledo (N.J.D.).
Correspondence to Dr Petra Schwarz, Department of Pharmacology, Johannes Gutenberg University, Obere Zahlbacher Strasse 67, 55101 Mainz, Germany. E-mail schwarz@mzdmza.zdv.uni-mainz.de.
Abstract This study was designed to elucidate whether nitric oxide (NO) controls norepinephrine (NE) release from sympathetic nerves of the rat heart. Hearts were perfused in the Langendorff mode with Tyrode's solution. The right sympathetic nerve was stimulated with trains of 1 or 3 Hz and NE release was measured. The NO synthase (NOS) inhibitor NG-nitro-L-arginine (L-NNA) enhanced the evoked NE release in a concentration-dependent manner. This facilitation was independent of the increase in perfusion pressure and was stereospecifically reversed by L-arginine but not D-arginine. Another NOS inhibitor, NG-methyl-L-arginine, produced a similar increase in NE release. The NO-donor compound S-nitroso-N-acetyl-D,L-penicillamine, added in the presence of L-NNA, restored the suppression of NE release in a concentration-dependent fashion. A similar suppression was achieved with 3-morpholinosydnonimine. These results demonstrated that NE release is under the inhibitory control of endogenous NO. Western blots demonstrated the presence of neuronal NOS I and endothelial NOS III in the hearts. Perfusion of the hearts with a low concentration of the detergent CHAPS produced functional damage of the endothelium, as evidenced by an increase in perfusion pressure and a conversion of the acetylcholine-induced coronary vasodilation to a constriction. However, CHAPS treatment did not produce a facilitation of NE release (as did the NOS inhibitors), and L-NNA still increased NE release in CHAPS-treated hearts. Double-labeling immunofluorescence histochemistry showed NOS I immunoreactivity in stellate ganglion cells and in neurons of the heart, some of which also stained positive for tyrosine hydroxylase. These findings suggest that NO, predominantly generated in neurons, controls NE release in the rat heart.
Key Words: NG-methyl-L-arginine • NG-nitro-L-arginine • S-nitroso-N-acetyl-D,L-penicillamine • CHAPS • 3-morpholinosydnonimine
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