Endogenous and Exogenous Nitric Oxide Inhibits Norepinephrine Release From Rat Heart Sympathetic Nerves

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.(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of intravenous sildenafil on hemodynamics and cardiac sympathetic activity in chronic human heart failure

“…First, nitric oxide (NO) is known to possess central sympathoinhibitory effects and sildenafil, by potentiating the biologic effects of NO, could reduce central sympathetic outflow [16,17]. Second, the prejunctional effects of NO on norepinephrine release could explain the cardiac sympathoinhibitory effect of sildenafil [18]. Finally, this selective cardiac sympathoinhibitory effect could be related to the cardiopulmonary baroreceptor unloading that occurred in response to sildenafil infusion.…”

Peroxynitrite is a positive inotropic agent in atrial and ventricular fibres of the frog heart

“…For example, the heterodimeric guanylyl cyclase andÏor cGMP-regulated proteins, may be more efficiently coupled to the inotropism in the atria, as compared with the ventricle. In addition, the cardiac autonomous system may play a permissive (or a suppressive) role on the effect of NO (Schwarz et al 1995), the extent of which may be different in the atria and the ventricle (Hartzell, 1988). These differences may result from the differential expression of the targets of the nitrogen species in the heart.…”

Nitric oxide and hypertension: not just an endothelium derived relaxing factor!

“…This may be due to pre-synaptic inhibition of noradrenaline release from cardiac sympathetic nerves. 71,72 The recent description of nNOS in the cardiac sarcoplasmic reticulum 73 may mean that this isoform also contributes to a post-synaptic inhibition of adrenergic signal transduction possibly by modulating intracellular calcium currents. 74 -76 Not all data on the cardiac effects of NO have been consistent.…”