NO synthase in cholinergic nerves and NO-induced relaxation in the rat isolated corpus cavernosum

Citation
P. Hedlund et al., NO synthase in cholinergic nerves and NO-induced relaxation in the rat isolated corpus cavernosum, BR J PHARM, 127(2), 1999, pp. 349-360
Citations number
43
Categorie Soggetti
Pharmacology & Toxicology
Journal title
BRITISH JOURNAL OF PHARMACOLOGY
ISSN journal
00071188 → ACNP
Volume
127
Issue
2
Year of publication
1999
Pages
349 - 360
Database
ISI
SICI code
0007-1188(199905)127:2<349:NSICNA>2.0.ZU;2-D
Abstract
1 In the rat corpus cavernosum (CC), the distribution of immunoreactivity f or neuronal and endothelial NO synthase (nNOS and eNOS), and the pattern of NOS-immunoreactive (-IR) nerves in relation to some other nerve population s, were investigated. Cholinergic nerves were specifically immunolabelled w ith antibodies to the vesicular acetylcholine transporter protein (VAChT). 2 In the smooth muscle septa surrounding the cavernous spaces, and around t he central and helicine arteries, the numbers of PGP- and tyrosine hydroxyl ase (TI-I)-IR terminals were large, whereas neuropeptide Y (NPY)-, VAChT-, nNOS-, and vasoactive intestinal polypeptide (VIP)-IR terminals were found in few to moderate numbers. 3 Double immunolabelling revealed that VAChT- and nNOS-IR terminals, VAChT- and VIP-IR terminals, nNOS-IR and VIP-IR terminals, and TH- and NPY-IR ter minals showed coinciding profiles, and co-existence was verified by confoca l laser scanning microscopy. TH immunoreactivity was not found in VAChT-, n NOS-, or VIP-IR nerve fibres or terminals. 4 An isolated strip preparation of the rat CC was developed, and characteri zed. In this preparation, cumulative addition of NO to noradrenaline (NA)-c ontracted strips, produced concentration-dependent, rapid, and almost compl ete relaxations. Electrical field stimulation of endothelin-I-contracted pr eparations produced frequency-dependent responses: a contractile twitch fol lowed by a fast relaxant response. After cessation of stimulation, there wa s a slow relaxant phase. Inhibition of NO synthesis, or blockade of guanyla te cyclase, abolished the first relaxant phase, whereas the second relaxati on was unaffected. 5 The results suggest that in the rat CC, nNOS, VAChT-, and VIP-immunoreact ivities can be found in the same parasympathetic cholinergic neurons. Inhib itory neurotransmission involves activation of the NO-system, and the relea se of other, as yet unknown, transmitters.