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Nitric oxide modulates sympathetic neurotransmission at the prejunctional level

Addicks, K., Bloch, W. and Feelisch, Martin (1994) Nitric oxide modulates sympathetic neurotransmission at the prejunctional level Microscopy Research and Technique, 29, (2), pp. 161-168. (PMID:7529070).

Record type: Article


In spite of accumulating evidence for a modulation of sympathetic neurotransmission by endogenously produced nitric oxide (NO), it remains unclear in which parts of the vascular system and at what level this interaction takes place. The aim of the present study was to investigate the distribution of endothelial and neuronal NO synthase (NOS) along the vascular tree of the heart at the light and electron microscopic level using NADPH-diaphorase (NADPH-d) staining as a marker for NOS. In addition, the functional effects of exogenous NO on coronary vascular resistance and cardiac adrenergic nerves was studied using the isolated perfused rat heart as a model. The intraaxonal catecholamine content of adrenergic nerve fibers was visualised and morphometrically assessed by applying glyoxylic acid-induced histofluorescence. The expression of endothelial NOS in the heart was found to depend on the diameter of the blood vessel. Arteries >100 ?m always showed intense staining, whereas staining in smaller arteries and veins was considerably weaker. Smooth-muscle free vessels were essentially devoid of NADPH-d activity. In atrial and ventricular myocardium, neuronal NOS localised in autonomic nerve fibers along the entire vascular tree. Ultrastructurally, NADPH-d staining revealed adjacent localisation of NOS-positive and -negative axons, suggesting an interaxonal modulation of adjacent autonomic nerve fibers by NO. In isolated perfused rat hearts, the intracoronary application of 10?8 M NO produced a marked decrease of coronary perfusion pressure, which was accompanied by a distinct increase in intraaxonal catecholamine levels of intramural adrenergic nerve fibers. These results suggest that the entire vascular system from arteries to veins is under the influence of NO and implies that two independently operating NO-driven processes are involved in the modulation of blood vessel tone: the well-known pathway of endothelium-derived NO acting directly on smooth muscle, and a second indirect pathway that inhibits noradrenaline release from perivascular nerve endings by endothelially or neuronally produced NO. The uneven distribution of endothelial NOS furthermore suggests that the latter mechanism predominates when the size of the blood vessel decreases

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Published date: 1 October 1994
Organisations: Clinical & Experimental Sciences


Local EPrints ID: 337902
ISSN: 1059-910X
PURE UUID: cc52f94a-c23d-48c4-a6f1-3407d7ca3c2e
ORCID for Martin Feelisch: ORCID iD

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Date deposited: 15 Aug 2012 10:13
Last modified: 30 Sep 2017 02:21

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Author: K. Addicks
Author: W. Bloch
Author: Martin Feelisch ORCID iD

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