SILDENAFIL, A TYPE-5 CGMP PHOSPHODIESTERASE INHIBITOR, SPECIFICALLY AMPLIFIES ENDOGENOUS cGMP-DEPENDENT RELAXATION IN RABBIT CORPUS CAVERNOSUM SMOOTH MUSCLE IN VITRO

Chuang, Alex T.; Strauss, John D.; Murphy, Richard A.; Steers, William D.

doi:10.1016/s0022-5347(01)63100-8

Cited by 133 publications

(45 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In vitro studies using human and rabbit cavernosal smooth muscles show that sildena®l signi®cantly increases cGMP concentrations and augments relaxation responses in the presence of SNP, but has little or no effect on phenylephrine-induced contractions when the tissues are not exposed to SNP or electrical ®eld stimulation [17,18]. However, in the present study treatment with sildena®l signi®cantly relaxed rabbit cavernosal muscle in a concentration-dependent manner, as reported by Stief et al [5].…”

Section: Discussionsupporting

confidence: 82%

“…Furthermore, Jeremy et al [20] reported that 10 mmol/L sildena®l alone increased the cGMP level up to ®ve-fold in rabbit corpus cavernosum tissue, and up to 28-fold in the presence of 1 mmol/L SNP. Reportedly, sildena®l alone signi®cantly reduced the basal tone in unstimulated rabbit cavernosal smooth muscle [18]. These in vitro and in vivo results suggest that signi®cant amounts of cGMP might be formed in the basal steady state in rabbit cavernosal smooth muscle.…”

Section: Discussionmentioning

confidence: 67%

See 1 more Smart Citation

Synergistic effects of sildenafil on relaxation of rabbit and rat cavernosal smooth muscles when combined with various vasoactive agents

Seo¹,

Kim²,

Jun³

et al. 2001

BJU International

View full text Add to dashboard Cite

Objective To evaluate which vasoactive agents have synergistic effects on the cavernosal smooth muscles of rabbits and rats when the agents are combined with sildena®l. Materials and methods Relaxation responses of cavernosal smooth muscle to single agents (phentolamine, moxisylyte, sodium nitroprusside, forskolin, vasoactive intestinal peptide, VIP, papaverine and sildena®l) in the rabbit, and prostaglandin-E 1 and sildena®l in the rat, and to combinations of each agent plus sildena®l, were assessed in vitro. The response to sildena®l of the rabbit strips with and without incubation with L-arginine (1 mmol/L) for 20 min was also evaluated. The effective concentrations for a half-maximal response of single agents and combination solutions were compared. Results All single agents induced concentrationdependent relaxation of the rabbit and rat cavernosal smooth muscles. There was signi®cant synergism on rabbit cavernosal smooth muscle when the sildena®l was combined with forskolin, sodium nitroprusside, VIP or phentolamine.There was also signi®cant synergism with sildena®l plus prostaglandin-E 1 in rat cavernosal muscles. There were no synergistic effects of combinations of sildena®l plus moxisylyte, papaverine or L-arginine.Conclusions These results suggest potentially effective combined therapies of sildena®l and intraurethral or intracavernosal prostaglandin-E 1 , intracavernosal forskolin or VIP, or oral phentolamine for patients with erectile dysfunction who have no success after monotherapy with these agents.

show abstract

Section: Discussionsupporting

confidence: 82%

Section: Discussionmentioning

confidence: 67%

Synergistic effects of sildenafil on relaxation of rabbit and rat cavernosal smooth muscles when combined with various vasoactive agents

Seo¹,

Kim²,

Jun³

et al. 2001

BJU International

View full text Add to dashboard Cite

show abstract

“…PDE-5 catalyzes the breakdown of the cGMP and also reduces NO levels in the endothelial cells, thereby decreasing signalling (Boswell-Smith et al 2006). The use of PDE-5 inhibitors such as sildenafil, tadalafil and verdanafil does not only raise the levels of cGMP (Chuang et al 1998;Corbin 2004) but also stimulates activation of cGMP and increases NO bioavailability for the relaxation of penile tissue that results in penile erection. However, these inhibitors also elicit several side effects, including headache, dyspepsia, nasal congestion, visual abnormalities among others (Saxena et al 2012).…”

Section: Discussionmentioning

confidence: 99%

Modulation of some markers of erectile dysfunction and malonaldehyde levels in isolated rat penile tissue with unripe and ripe plantain peels: identification of the constituents of the plants using HPLC

Oboh

Ademiluyi

Oyeleye

et al. 2017

Pharmaceutical Biology

View full text Add to dashboard Cite

“…2,3 Sildena®l, a widely prescribed oral medication for the treatment of male erectile dysfunction, is a selective and highly potent inhibitor of the type-5 cGMP-speci®c phosphodiesterase. 4 Type-5 PDE isozyme is predominantly expressed in the penile corpus cavernosum, however it has been localized in various other tissues, such as brain, lung, kidney and placenta. 5 Although little is known about the physiological role of PDE and its isoforms in human spermatozoa, its inhibition has been reported to stimulate sperm motility, suggesting an association between the levels of cytosolic nucleotides and sperm motion.…”

Section: Introductionmentioning

confidence: 99%

The effect of sildenafil on human sperm motion and function from normal and infertile men

et al. 2000

View full text Add to dashboard Cite

The aim of this report was to study the effect of sildena®l, a speci®c type-5 phosphodiesterase inhibitor, on human sperm motility, viability, membrane integrity and sperm penetration assay.Spermatozoa were obtained from normal donors (n 6) and infertile men (n 6) were washed using a single Percoll (80%) gradient, suspended in Ham's F-10 medium, and incubated with various doses of sildena®l (125, 250 and 750 ngaml); pentoxifylline (3 mM) was used as a positive control, and Ham's F-10 was used as a reagent control. Sperm motility, grade, viability, membrane integrity (by hypo-osmotic swelling test), and motion evaluation were carried out at various time intervals. Hamster ova sperm penetration assay (SPA) was used to evaluate overall sperm function.Sildena®l did not affect sperm motility, viability or membrane integrity under these conditions as compared to our Ham's control (P b 0.05). Incubation with pentoxifylline signi®cantly enhanced sperm motility (P`0.05) and viability without affecting membrane integrity (P`0.05). Sperm incubated with sildena®l and pentoxifylline from both normal donors and infertile patients demonstrated no signi®cant change in sperm penetration assay from respective controls.In conclusion, sildena®l, at the doses evaluated, did not signi®cantly alter the motility, viability, membrane integrity or sperm penetration characteristics of human spermatozoa from normal donors and infertile patients.

show abstract

SILDENAFIL, A TYPE-5 CGMP PHOSPHODIESTERASE INHIBITOR, SPECIFICALLY AMPLIFIES ENDOGENOUS cGMP-DEPENDENT RELAXATION IN RABBIT CORPUS CAVERNOSUM SMOOTH MUSCLE IN VITRO

Abstract: Sildenafil relaxes CCSM by amplifying the effects of the normal, endogenous cGMP dependent relaxation mechanisms.

Cited by 133 publications

References 22 publications

Synergistic effects of sildenafil on relaxation of rabbit and rat cavernosal smooth muscles when combined with various vasoactive agents

Synergistic effects of sildenafil on relaxation of rabbit and rat cavernosal smooth muscles when combined with various vasoactive agents

Modulation of some markers of erectile dysfunction and malonaldehyde levels in isolated rat penile tissue with unripe and ripe plantain peels: identification of the constituents of the plants using HPLC

The effect of sildenafil on human sperm motion and function from normal and infertile men

Contact Info

Product

Resources

About