Effect of Low Androgen Status on the Expression of P2Y Receptors in the Corpus Cavernosum of Rats

Liu, Pan; Jiang, Jun; Xia, Jianguo; Jiang, Rui

doi:10.1016/j.urology.2018.03.018

Cited by 7 publications

(5 citation statements)

References 24 publications

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“…In castration groups, bilateral rat testicles were removed. Castration + T groups were subcutaneously injected with 3mg/kg T propionate (Renjian Pharmaceutical Co. Ltd., Ningbo, China) every other day starting from the second day after the operation, and the rest of the groups were subcutaneously injected with the same amount of vegetable oil (Yihai Kerry Co. Ltd., Shanghai, China) 17 . All experimental procedures followed the Guidelines of the Chinese Society of Laboratory Animals and the Guide for the Care and Use of Laboratory Animals (US National Institutes of Health Publication No 85‐23, revised 1996).…”

Section: Methodsmentioning

confidence: 99%

Low androgen status inhibits erectile function by inducing eNOS uncoupling in rat corpus cavernosum

et al. 2020

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Background The number of erectile dysfunction (ED) patients is increasing annually. How to improve the effectiveness of ED treatment is an important issue for the field of andrology. Objectives To investigate whether low androgen status impairs the erectile function of rats by regulated endothelial nitric oxide synthase (eNOS) uncoupling. Materials and methods Thirty‐six 8‐week‐old male Sprague Dawley (SD) rats were randomly divided into six groups as follows: 4‐week sham‐operated group (4w‐sham), 4‐week castration group (4w‐cast), 4‐week castration + testosterone (T) group (4w‐cast + T), 8‐week sham‐operated group (8w‐sham), 8‐week castration group (8w‐cast), and 8‐week castration + T group (8w‐cast + T). Three mg/kg of T was subcutaneously injected every other day in castration + T groups. The ratio of the maximum intracavernous pressure/the mean arterial pressure (ICPmax/MAP), the level of serum T, dihydrobiopterin(BH2), tetrahydrobiopterin (BH4), nitric oxygen(NO), 3‐nitrotyrosine(3NT), dihydrofolate reductase (DHFR), guanosine triphosphate cyclohydrolase 1 (GTPCH1), nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2), and eNOS monomers/dimers in the corpus cavernosum were detected. Results The ratio of ICPmax/MAP and BH4/BH2, the level of serum T, NO, and GTPCH1 decreased significantly in castration groups compared with sham‐operated groups and castration + T groups (P < .05) and decreased significantly in 8w‐cast group compared with 4w‐cast group (P < .05). The expression of 3NT and NOX2 and the ratio of eNOS monomers/dimers increased significantly in castration groups compared with sham‐operated groups and castration + T groups (P < .01) and increased significantly in 8w‐cast group compared with 4w‐cast group (P < .01). The expression of DHFR in 4w‐cast group was significantly higher than that in 4w‐sham group and 4w‐cast + T group (P < .01) and in 8w‐cast group was significantly lower than that in 8w‐sham group and 8w‐cast + T group (P < .01). Discussion and Conclusion Low androgen status induces eNOS uncoupling by reducing BH4/BH2 and increasing 3NT. Due to the decreased NO production, the erectile function of the rats was impaired.

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Section: Methodsmentioning

confidence: 99%

Low androgen status inhibits erectile function by inducing eNOS uncoupling in rat corpus cavernosum

et al. 2020

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“…The weight of the rats was measured. According to our previous method, 16 a 26G needle filled with heparin saline was used to puncture the right common carotid artery and connect it to a pressure sensor (BL‐420s biological function experiment system, Chengdu Instrument Factory, China) to continuously monitor the mean arterial pressure (MAP) of the common carotid artery. A 24G needle filled with heparin saline was inserted into the cavernous body and connected to a pressure sensor to measure intracorporeal pressure (ICP).…”

Section: Methodsmentioning

confidence: 99%

Icariin modulates eNOS activity via effect on post‐translational protein‐protein interactions to improve erectile function of spontaneously hypertensive rats

et al. 2020

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Background Type 5 phosphodiesterase inhibitor (PDE5I) has become the first‐line treatment for erectile dysfunction (ED). However, its effective rate for hypertension ED is only 60%‐70%. How to improve the efficacy of ED treatment is the focus of current research. Objective To explore whether icariin can improve the erectile function of spontaneously hypertensive rats (SHR) by affecting post‐translational protein‐protein interactions to regulate endothelial nitric oxide synthetase (eNOS) activity. Method Twelve‐week‐old healthy male SHR rats and Wistar‐Kyoto rats (WKY) were randomly divided into four groups: SHR control group, SHR + icariin (10 mg/kg·d gavage) treatment group, WKY control group, and WKY + icariin (10 mg/kg·d gavage) treatment group (n = 5). After 4 weeks, the maximum penile intracavernous pressure/mean arterial pressure (ICPmax/MAP), the expression of heat‐shock protein 90 (Hsp90), caveolin‐1, calmodulin, p‐eNOS, and eNOS in penile cavernous tissue and the content of nitric oxide (NO) and cGMP were measured. The interaction between eNOS and Hsp90, caveolin‐1, and calmodulin were detected by immunoprecipitation. Result The ICPmax/MAP in the SHR + icariin treatment group (0.08 ± 0.01, 0.23 ± 0.07, 0.40 ± 0.05) was significantly higher than the SHR group (0.03 ± 0.01, 0.13 ± 0.03, 0.21 ± 0.02) under 3V and 5V electrical stimulations (P < .05). Compared with the SHR group, the expression of HSP90, calmodulin, P‐eNOS, eNOS, and P‐eNOS/eNOS in the penile cavernous tissue of rats in the WKY group and the SHR + icariin treatment group were significantly increased (P < .05), and the expression of caveolin‐1 was significantly decreased (P < .05). The NO content (2.16 ± 0.22 μmol/g) and cGMP concentration (3.69 ± 0.12 pmol/mg) in the SHR + icariin treatment group were significantly higher than those in the SHR group (1.01 ± 0.14 μmol/g, 2.31 ± 0.22 pmol/mg) (P < .05). Compared with the SHR group, the interaction between eNOS and HSP90 in the cavernosa of the rats in the SHR + icariin treatment group was significantly increased (P < .05), the interaction between eNOS and caveolin‐1 was significantly decreased (P < .01), and the interaction between eNOS and calmodulin did not significantly change. Discussion and Conclusion Up‐regulating the expression of HSP90 and calmodulin and inhibiting caveolin‐1 in SHR corpus cavernosum, promoting the interaction between eNOS and HSP90, inhibiting the interaction between eNOS and caveolin‐1, increasing p‐eNOS/eNOS, may be the mechanism of icariin that improves SHR erectile function.

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“…The rats in the androgen replacement groups were subcutaneously injected with 3 mg/kg of testosterone propionate (Double‐Crane Pharmaceutical Company) every other day after castration. Rats in the other groups were injected with the same volume of vegetable oil (Liu, Jiang, Xia, & Jiang, ). All procedures involving animals were performed following the Guide for the Care and Use of Laboratory Animals (NIH Publication No 85‐23, revised 1996).…”

Section: Methodsmentioning

confidence: 99%

“…After 4 and 8 weeks from surgery, the rats were anesthetised with 40 mg/kg of 1% pentobarbital sodium intraperitoneally. According to our previous method (Li, Jiang, Xia, & Jiang, ; Liu et al, ), the heparin‐filled 26G and 24G needles were respectively inserted into the right common carotid artery and corpus cavernosum and then connected with pressure transducers and BL‐420s Biological Function Experiment System (TechMan Technology Co., Ltd). After completing an abdominal midline incision, the major pelvic ganglion which is located in the posterior side of the prostate was found and electrically stimulated.…”

Section: Methodsmentioning

confidence: 99%

Effect of low androgen status on the expression of adenosine A _2A and A _2B receptors in rat penile corpus cavernosum

et al. 2019

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To investigate whether low androgen status affects erectile function by regulating the expression of adenosine A2A and A2B receptors in rat penile corpus cavernosum. Thirty‐six 8‐week‐old male Sprague‐Dawley rats were randomly divided into six groups: sham‐operated group (4w‐sham, 8w‐sham), castration group (4w‐cast, 8w‐cast) and androgen replacement group (4w‐cast+T, 8w‐cast+T). The rats in the androgen replacement groups were subcutaneously injected with testosterone propionate (3 mg/kg) every other day after castration. The maximum intracavernous pressure/mean arterial pressure (ICPmax/MAP), the expression of A2A, A2B, AKT and eNOS and the concentrations of cAMP and cGMP in the corpus cavernosum were detected at the 4th and 8th weeks after the operation. The serum testosterone level and the ratio of ICPmax/MAP decreased significantly in the castration group as compared to other groups (p < 0.01). There was no significant difference in the expression of A2A receptor among groups, while the expression of A2B, AKT and eNOS and the concentrations of cAMP and cGMP in the castration group were significantly lower than in other groups (p < 0.01). Low androgen status inhibits the AKT/eNOS/cGMP signalling pathways and the production of cAMP in the corpus cavernosum of castrated rats by down‐regulating the expression of A2B receptor, and results in decreased of ICPmax/MAP.

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Effect of Low Androgen Status on the Expression of P2Y Receptors in the Corpus Cavernosum of Rats

Cited by 7 publications

References 24 publications

Low androgen status inhibits erectile function by inducing eNOS uncoupling in rat corpus cavernosum

Low androgen status inhibits erectile function by inducing eNOS uncoupling in rat corpus cavernosum

Icariin modulates eNOS activity via effect on post‐translational protein‐protein interactions to improve erectile function of spontaneously hypertensive rats

Effect of low androgen status on the expression of adenosine A _2A and A _2B receptors in rat penile corpus cavernosum

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Effect of Low Androgen Status on the Expression of P2Y Receptors in the Corpus Cavernosum of Rats

Cited by 7 publications

References 24 publications

Low androgen status inhibits erectile function by inducing eNOS uncoupling in rat corpus cavernosum

Low androgen status inhibits erectile function by inducing eNOS uncoupling in rat corpus cavernosum

Icariin modulates eNOS activity via effect on post‐translational protein‐protein interactions to improve erectile function of spontaneously hypertensive rats

Effect of low androgen status on the expression of adenosine A 2A and A 2B receptors in rat penile corpus cavernosum

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Effect of low androgen status on the expression of adenosine A _2A and A _2B receptors in rat penile corpus cavernosum