Insulin-Like Growth Factor-1 Restores Erectile Function in Aged Rats: Modulation the Integrity of Smooth Muscle and Nitric Oxide-Cyclic Guanosine Monophosphate Signaling Activity

2008 ◽  
Vol 5 (6) ◽  
pp. 1345-1354 ◽  
Author(s):  
Xiao-Yong Pu ◽  
Xing-Huan Wang ◽  
Wai-Chen Gao ◽  
Zhong-Hua Yang ◽  
Shi-Lin Li ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Smooth Muscle ◽  
Growth Factor ◽  
Erectile Function ◽  
Cyclic Guanosine Monophosphate ◽  
Guanosine Monophosphate ◽  
Insulin Like Growth Factor ◽  
Aged Rats ◽  
Signaling Activity

scholarly journals Mesenchymal Stem Cells Modified With Short Hairpin RNA (shRNA) Constructs Targeting Insulin-like Growth Factor Binding Protein-3 (IGFBP-3) Improve Erectile Dysfunction in old Rats

2020 ◽  
Author(s):  
Xiao-Yong Pu ◽  
Xie-WU Zhang ◽  
Xuang-Xue Zhou ◽  
Jian-Xiong Fang ◽  
Hao-Sheng Liu ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Growth Factor ◽  
Treatment Group ◽  
Erectile Function ◽  
Corpus Cavernosum ◽  
Insulin Like Growth Factor ◽  
Hairpin Rna ◽  
Old Rats ◽  
Short Hairpin ◽  
Igfbp 3

Abstract Background: We have confirmed that injection of vector-based short hairpin RNA (shRNA) constructs targeting insulin-like growth factor binding protein-3 (IGFBP-3) in penis in old rat can improve erectile function. The aim of this study is to further determine the feasibility of bone marrowe derived mesenchymal stem cells (BM-MSCs) genetically modified with shRNA constructs targeting IGFBP-3 on improving erectile function in the aged rat. Methods: 40 old (24 months) male rats were randomized divided into 4 groups: PBS-only, BM-MSC treatment and LV3-shIGFBP-3 engineered BM-MSC treatment group (n=10/group).Ten 5-month-old rats were used as the young group. Four weeks after transplantation, the erectile function was assessed by cavernosal nerve stimulation. The percent of smooth muscle in corpus cavernosum was evaluated by masson’s trichrome staining. IGFBP-3 expression was estimated by Western blot. The cavernous insulin-like growth factor-1 (IGF-1) and vascular endothelial growth factor (VEGF) levels were analyzed after transplantation. Apoptosis in corpus cavernosum was measured using TUNEL and the activity of nitric oxide synthase (NOS) and concentration of guanosine 3’, 5’-cyclic-monophosphates (cGMP) in penile tissue were also analyzed. Results: Four weeks after intracavernous injection, BM-MSCs alone, especially LV3-shIGFBP-3 engineered BM-MSCs treatment rats had improvements in erectile function (p<0.05). The percentage of cavernosal smooth muscle was increased in BM-MSCs and LV3-shIGFBP-3 engineered BM-MSCs treatment group. IGFBP-3 protein expression was decreased obviously after injection of LV3-shIGFBP-3 engineered BM-MSCs. In addition, significant lower IGFBP-3 expression was associated with increased IGF-1 expression in LV3-shIGFBP-3 engineered BM-MSCs treatment rats although higher IGF-1 and VEGF concentrations were all determined after transplantation with BM-MSCs alone or BM-MSCs modified with LV3-shIGFBP-3. Lower levels of the apoptosis were also observed in the BM-MSCs and LV3-shIGFBP-3 engineered BM-MSCs treatment group. NOS activities and cGMP concentrations were also significantly increased after transplantation. Conclusions: These findings demonstrate that BM-MSCs alone or genetically modified with LV3-shIGFBP-3 can improve diminished erectile responses in the aged rat partially by increasing the smooth muscle integrity, increasing secretion of IGF-1 and VEGF, inhibiting apoptosis and increasing the NOS activity and cGMP accumulation.

Nitric oxide and regulation of vascular tone: pharmacological and physiological considerations

1998 ◽  
Vol 7 (2) ◽  
pp. 131-140 ◽  
Author(s):  
J McHugh ◽  
DJ Cheek
Keyword(s):  
Nitric Oxide ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Vascular System ◽  
Biological Activities ◽  
Vascular Diseases ◽  
Cyclic Guanosine Monophosphate ◽  
Guanosine Monophosphate ◽  
Physical Stimuli ◽  
Artery Disease

The endothelial cells of the vascular system are responsible for many biological activities that maintain vascular homeostasis. Responding to a variety of chemical and physical stimuli, the endothelium elaborates a host of vasoactive agents. One of these agents, endothelium-derived relaxing factor, now accepted as nitric oxide, influences both cellular constituents of the blood and vascular smooth muscle. A principal intracellular target for nitric oxide is guanylate cyclase, which, when activated, increases the intracellular concentration of cyclic guanosine monophosphate, which in turn activates protein kinase G. Acting by this pathway, nitric oxide induces relaxation of vascular smooth muscle and inhibits platelet activation and aggregation. Derangements in endothelial production of nitric oxide are implicated as both cause and consequence of vascular diseases, including hypertension, atherosclerosis, and coronary artery disease.

scholarly journals Synthesis and Modeling Studies of Furoxan Coupled Spiro-Isoquinolino Piperidine Derivatives as NO Releasing PDE 5 Inhibitors

Biomedicines ◽  
2020 ◽  
Vol 8 (5) ◽  
pp. 121
Author(s):  
Swami Prabhuling ◽  
Yasinalli Tamboli ◽  
Prafulla B. Choudhari ◽  
Manish S. Bhatia ◽  
Tapan Kumar Mohanta ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Smooth Muscle ◽  
Soluble Guanylate Cyclase ◽  
Corpus Cavernosum ◽  
Active Role ◽  
Cyclic Guanosine Monophosphate ◽  
Guanosine Monophosphate ◽  
Molecular Modelling Studies ◽  
Modelling Studies ◽  
Muscle Relaxant Activity

Nitric oxide (NO) is considered to be one of the most important intracellular messengers that play an active role as neurotransmitter in regulation of various cardiovascular physiological and pathological processes. Nitric oxide (NO) is a major factor in penile erectile function. NO exerts a relaxing action on corpus cavernosum and penile arteries by activating smooth muscle soluble guanylate cyclase and increasing the intracellular concentration of cyclic guanosine monophosphate (cGMP). Phophodiesterase (PDE) inhibitors have potential therapeutic applications. NO hybridization has been found to improve and extend the pharmacological properties of the parental compound. The present study describes the synthesis of novel furoxan coupled spiro-isoquinolino-piperidine derivatives and their smooth muscle relaxant activity. The study reveals that, particularly 10d (1.50 ± 0.6) and 10g (1.65 ± 0.7) are moderate PDE 5 inhibitors as compared to Sidenafil (1.43 ± 0.5). The observed effect was explained by molecular modelling studies on phosphodiesterase.

scholarly journals Mesenchymal Stem Cells Modified with Short Hairpin RNA (shRNA) Constructs Targeting Insulin-like Growth Factor Binding Protein-3 (IGFBP-3) Improve Erectile Dysfunction in Old Rats

2020 ◽  
Author(s):  
Xiao-Yong Pu ◽  
Xie-WU Zhang ◽  
Xuang-Xue Zhou ◽  
Jian-Xiong Fang ◽  
Hao-Sheng Liu ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Growth Factor ◽  
Treatment Group ◽  
Erectile Function ◽  
Corpus Cavernosum ◽  
Insulin Like Growth Factor ◽  
Hairpin Rna ◽  
Old Rats ◽  
Short Hairpin ◽  
Igfbp 3

Abstract Background: We have confirmed that injection of vector-based short hairpin RNA (shRNA) constructs targeting insulin-like growth factor binding protein-3 (IGFBP-3) in penis in old rat can improve erectile function. The aim of this study is to further determine the feasibility of bone marrowe derived mesenchymal stem cells (BM-MSCs) genetically modified with shRNA constructs targeting IGFBP-3 on improving erectile function in the aged rat. Methods: 40 old (24 months) male rats were randomized divided into 4 groups: PBS-only, BM-MSC treatment and LV3-shIGFBP-3 engineered BM-MSC treatment group (n=10/group).Ten 5-month-old rats were used as the young group. Four weeks after transplantation, the erectile function was assessed by cavernosal nerve stimulation. The percent of smooth muscle in corpus cavernosum was evaluated by masson’s trichrome staining. IGFBP-3 expression was estimated by Western blot. The cavernous insulin-like growth factor-1 (IGF-1) and vascular endothelial growth factor (VEGF) levels were analyzed after transplantation. Apoptosis in corpus cavernosum was measured using TUNEL and the activity of nitric oxide synthase (NOS) and concentration of guanosine 3’, 5’-cyclic-monophosphates (cGMP) in penile tissue were also analyzed. Results: Four weeks after intracavernous injection, BM-MSCs alone, especially LV3-shIGFBP-3 engineered BM-MSCs treatment rats had improvements in erectile function (p<0.05). The percentage of cavernosal smooth muscle was increased in BM-MSCs and LV3-shIGFBP-3 engineered BM-MSCs treatment group. IGFBP-3 protein expression was decreased obviously after injection of LV3-shIGFBP-3 engineered BM-MSCs. In addition, significant lower IGFBP-3 expression was associated with increased IGF-1 expression in LV3-shIGFBP-3 engineered BM-MSCs treatment rats although higher IGF-1 and VEGF concentrations were all determined after transplantation with BM-MSCs alone or BM-MSCs modified with LV3-shIGFBP-3. Lower levels of the apoptosis were also observed in the BM-MSCs and LV3-shIGFBP-3 engineered BM-MSCs treatment group. NOS activities and cGMP concentrations were also significantly increased after transplantation. Conclusions: These findings demonstrate that BM-MSCs alone or genetically modified with LV3-shIGFBP-3 can improve diminished erectile responses in the aged rat partially by increasing the smooth muscle integrity, increasing secretion of IGF-1 and VEGF, inhibiting apoptosis and increasing the NOS activity and cGMP accumulation.

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