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Nitric oxide independent activation of guanylate cyclase by YC-1 causes erectile responses in the rat.

Mizusawa, H; Hedlund, Petter LU ; Brioni, J D; Sullivan, J P and Andersson, Karl-Erik LU (2002) In Journal of Urology 167(5). p.2276-2281
Abstract
PURPOSE: Activation of soluble guanylate cyclase with a subsequent increase in intracellular levels of cyclic guanosine monophosphate is necessary for normal erection. In vascular tissue 3(5'-hydroxymethyl-2'-furyl-1-benzyl indazole (YC-1) (Abbott Laboratories, North Chicago, Illinois) has been shown to stimulate soluble guanylate cyclase independent of nitric oxide. We studied whether YC-1 modulates erectile responses in the rat. MATERIALS AND METHODS: The effects of YC-1 given intracavernously or intraperitoneally on intracavernous pressure were investigated in rats. Functional effects of YC-1 on neuronal and endothelial nitric oxide relaxations were studied in 3 x 10(-6) M. 1-noradrenaline contracted preparations of rat isolated corpus... (More)
PURPOSE: Activation of soluble guanylate cyclase with a subsequent increase in intracellular levels of cyclic guanosine monophosphate is necessary for normal erection. In vascular tissue 3(5'-hydroxymethyl-2'-furyl-1-benzyl indazole (YC-1) (Abbott Laboratories, North Chicago, Illinois) has been shown to stimulate soluble guanylate cyclase independent of nitric oxide. We studied whether YC-1 modulates erectile responses in the rat. MATERIALS AND METHODS: The effects of YC-1 given intracavernously or intraperitoneally on intracavernous pressure were investigated in rats. Functional effects of YC-1 on neuronal and endothelial nitric oxide relaxations were studied in 3 x 10(-6) M. 1-noradrenaline contracted preparations of rat isolated corpus cavernosum. RESULTS: Intracavernous YC-1 (10 micromol. kg.-1) produced erectile responses with a mean intracavernous pressure plus or minus standard error of mean of 81 +/- 17 cm. water (p <0.001) and a mean duration of 7.1 +/- 3.3 minutes (p <0.001). YC-1 (10 micromol. kg.-1) given intraperitoneally also increased the amplitude and duration of erectile responses to cavernous nerve stimulation. Mean peak intracavernous pressure increased from 63 +/- 6 to 10(2) +/- 16 cm. water (p <0.05). Erections induced by a submaximal dose of 25 microg. kg.-1 apomorphine s.c. increased in number after 10 micromol. kg.-1 YC-1 intraperitoneally (p <0.05). In vitro nerve induced relaxant responses were enhanced by increasing concentrations of YC-1. Relaxations at 20 Hz. were increased from a mean of 9% +/- 5% to 52% +/- 5% at a YC-1 concentration of 10(-5) M. (p <0.001). At this concentration carbachol induced relaxations were enhanced from a mean of 19% +/- 3% to 40% +/- 9% (p <0.05). CONCLUSIONS: YC-1 can evoke erectile responses when given intracavernously and it enhances erections induced by cavernous nerve stimulation and apomorphine when given systemically. In vitro YC-1 enhances electrically evoked relaxations in rat corpus cavernosum. YC-1 represents an interesting pharmacological principle that may be useful for treating erectile dysfunction. (Less)
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keywords
Guanylate Cyclase : metabolism, Enzyme Activators : pharmacology, Drug, Hydrostatic Pressure, Indazoles : pharmacology, Penile Erection : drug effects, Nitric Oxide : physiology, Male, Intraperitoneal, Injections, Penile Erection : physiology, Penis : drug effects, Dose-Response Relationship, Comparative Study, Animal, Apomorphine : pharmacology
in
Journal of Urology
volume
167
issue
5
pages
2276 - 2281
publisher
Lippincott Williams & Wilkins
external identifiers
  • wos:000174963900093
  • pmid:11956492
  • scopus:0036227586
ISSN
1527-3792
DOI
10.1016/S0022-5347(05)65142-7
language
English
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yes
id
5b93ebe8-1a3c-4b7b-b98b-4c3ff64a4b10 (old id 107705)
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http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11956492&dopt=Abstract
date added to LUP
2007-07-05 14:03:33
date last changed
2017-01-01 06:57:29
@article{5b93ebe8-1a3c-4b7b-b98b-4c3ff64a4b10,
  abstract     = {PURPOSE: Activation of soluble guanylate cyclase with a subsequent increase in intracellular levels of cyclic guanosine monophosphate is necessary for normal erection. In vascular tissue 3(5'-hydroxymethyl-2'-furyl-1-benzyl indazole (YC-1) (Abbott Laboratories, North Chicago, Illinois) has been shown to stimulate soluble guanylate cyclase independent of nitric oxide. We studied whether YC-1 modulates erectile responses in the rat. MATERIALS AND METHODS: The effects of YC-1 given intracavernously or intraperitoneally on intracavernous pressure were investigated in rats. Functional effects of YC-1 on neuronal and endothelial nitric oxide relaxations were studied in 3 x 10(-6) M. 1-noradrenaline contracted preparations of rat isolated corpus cavernosum. RESULTS: Intracavernous YC-1 (10 micromol. kg.-1) produced erectile responses with a mean intracavernous pressure plus or minus standard error of mean of 81 +/- 17 cm. water (p &lt;0.001) and a mean duration of 7.1 +/- 3.3 minutes (p &lt;0.001). YC-1 (10 micromol. kg.-1) given intraperitoneally also increased the amplitude and duration of erectile responses to cavernous nerve stimulation. Mean peak intracavernous pressure increased from 63 +/- 6 to 10(2) +/- 16 cm. water (p &lt;0.05). Erections induced by a submaximal dose of 25 microg. kg.-1 apomorphine s.c. increased in number after 10 micromol. kg.-1 YC-1 intraperitoneally (p &lt;0.05). In vitro nerve induced relaxant responses were enhanced by increasing concentrations of YC-1. Relaxations at 20 Hz. were increased from a mean of 9% +/- 5% to 52% +/- 5% at a YC-1 concentration of 10(-5) M. (p &lt;0.001). At this concentration carbachol induced relaxations were enhanced from a mean of 19% +/- 3% to 40% +/- 9% (p &lt;0.05). CONCLUSIONS: YC-1 can evoke erectile responses when given intracavernously and it enhances erections induced by cavernous nerve stimulation and apomorphine when given systemically. In vitro YC-1 enhances electrically evoked relaxations in rat corpus cavernosum. YC-1 represents an interesting pharmacological principle that may be useful for treating erectile dysfunction.},
  author       = {Mizusawa, H and Hedlund, Petter and Brioni, J D and Sullivan, J P and Andersson, Karl-Erik},
  issn         = {1527-3792},
  keyword      = {Guanylate Cyclase : metabolism,Enzyme Activators : pharmacology,Drug,Hydrostatic Pressure,Indazoles : pharmacology,Penile Erection : drug effects,Nitric Oxide : physiology,Male,Intraperitoneal,Injections,Penile Erection : physiology,Penis : drug effects,Dose-Response Relationship,Comparative Study,Animal,Apomorphine : pharmacology},
  language     = {eng},
  number       = {5},
  pages        = {2276--2281},
  publisher    = {Lippincott Williams & Wilkins},
  series       = {Journal of Urology},
  title        = {Nitric oxide independent activation of guanylate cyclase by YC-1 causes erectile responses in the rat.},
  url          = {http://dx.doi.org/10.1016/S0022-5347(05)65142-7},
  volume       = {167},
  year         = {2002},
}