4.7 Article

Morphological and functional in vitro and in vivo characterization of the mouse corpus cavernosum

Journal

BRITISH JOURNAL OF PHARMACOLOGY
Volume 132, Issue 6, Pages 1333-1341

Publisher

WILEY
DOI: 10.1038/sj.bjp.0703938

Keywords

penile erection; nitric oxide; cyclic GMP; cholinergic; peptides; nerves; relaxation; sildenafil; in vivo; mouse

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1 In normal mice, the distribution of adrenergic, cholinergic, some peptidergic, and neuronal nitric oxide synthase (nNOS)-containing nerves were investigated. Functional in vitro correlates were obtained. An in viva model was developed in which erectile haemodynamics in response to drugs or nerve-stimulation were studied. 2 Immunoreactivities for vesicular acetylcholine transporter protein (VAChT), nNOS-, and vasoactive intestinal polypeptide (VIP), co-existed in nerve fibres and terminal varicosities. Immunoreactivities for neuropeptide Y (NPY) and tyrosine hydroxylase (TH) were found in the same nerve structures. 3 Chemical sympathectomy abolished TH- and NPY-IR nerve structures in cavernous smooth muscle bundles. The distribution of calcitonin gene-related peptide (CGRP)-, nNOS-, VAChT- and VIP-IR nerve structures was unchanged. 4 In endothelial cells of the central and helicine arteries, veins and venules, intense immunoreactivity for endothelial NOS (eNOS) was observed. No distinct eNOS-IR cells were found lining the cavernous sinusoids. 5 in vitro, nerve-induced relaxations were verified, and endothelial NO/cyclic GMP-mediated relaxant responses were established. VIP and CGRP had small relaxant effects. A functioning adenylate cyclase/cyclic AMP pathway was confirmed. 6 Neuronal excitatory responses were abolished by prazosin, or forskolin. VIP and CGRP counteracted contractions, whereas NPY and scopolamine enhanced excitatory responses. 7 In vivo, erectile responses were significantly attenuated by L-NAME (50 mg kg(-1)) and facilitated by sildenafil (200 mug kg(-1)). 8 It is concluded that the mouse is a suitable model for studies of erectile mechanisms in vitro and in vivo.

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