Nitric oxide independent activation of guanylate cyclase by YC-1 causes erectile responses in the rat.
| العنوان: | Nitric oxide independent activation of guanylate cyclase by YC-1 causes erectile responses in the rat. |
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| المؤلفون: | Mizusawa, H, Hedlund, Petter, Brioni, J D, Sullivan, J P, Andersson, Karl-Erik |
| المصدر: | Journal of Urology. 167(5):2276-2281 |
| مصطلحات موضوعية: | 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, Medicin och hälsovetenskap, Klinisk medicin, Urologi och njurmedicin, Medical and Health Sciences, Clinical Medicine, Urology and Nephrology |
| الوصف: | 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. |
| URL الوصول: | https://lup.lub.lu.se/record/107705 http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11956492&dopt=Abstract http://dx.doi.org/10.1016/S0022-5347(05)65142-7 |
| قاعدة البيانات: | SwePub |
| تدمد: | 15273792 |
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| DOI: | 10.1016/S0022-5347(05)65142-7 |