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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/107705
- author
- Mizusawa, H
; Hedlund, Petter
LU
; Brioni, J D
; Sullivan, J P
and Andersson, Karl-Erik
LU
- organization
- publishing date
- 2002
- type
- Contribution to journal
- publication status
- published
- subject
- 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
- LU publication?
- yes
- id
- 5b93ebe8-1a3c-4b7b-b98b-4c3ff64a4b10 (old id 107705)
- alternative location
- http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11956492&dopt=Abstract
- date added to LUP
- 2016-04-01 16:09:45
- date last changed
- 2022-01-28 17:44:34
@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 <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.}},
author = {{Mizusawa, H and Hedlund, Petter and Brioni, J D and Sullivan, J P and Andersson, Karl-Erik}},
issn = {{1527-3792}},
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}},
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}},
doi = {{10.1016/S0022-5347(05)65142-7}},
volume = {{167}},
year = {{2002}},
}