Inhibitors of phosphodiesterase 5 (PDE 5) inhibit the nerve‐induced release of nitric oxide from the rabbit corpus cavernosum

Hallén, Katarina; Wiklund, Peter; Gustafsson, Lars E.

doi:10.1038/sj.bjp.0706991

Cited by 15 publications

(14 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The concentrations at which alfuzosin exerted this enhancing effect were in the same range than its pKi value (8.2) determined in binding studies against α1‐adrenoceptors [42,43]. The relaxing effect of tadalafil on precontracted corpus cavernosum strips is in accordance with several studies, which previously investigated the relaxant properties of tadalafil in human [24] or in rabbit cavernosal strips [44,45]. Numerous studies have also previously evidenced that α1‐adrenoceptor antagonists could modulate corpus cavernosum contractile tone [31,46–48].…”

Section: Discussionsupporting

confidence: 79%

Combination of Alfuzosin and Tadalafil Exerts In Vitro an Additive Relaxant Effect on Human Corpus Cavernosum

Oger¹,

Behr‐Roussel²,

Gorny³

et al. 2008

The Journal of Sexual Medicine

View full text Add to dashboard Cite

Introduction Phosphodiesterase type 5 (PDE5) inhibitors, such as tadalafil, are a first-line treatment for erectile dysfunction (ED). Nevertheless, some patients do not respond to this treatment. Clinical data suggest that the addition of α1-adrenoceptor blocker, such as alfuzosin, commonly prescribed for lower urinary tract symptoms suggestive of benign prostatic hyperplasia, may be of benefit. Aim Evaluation of the effect of alfuzosin, tadalafil or the combination of both on human corpus cavernosum. Methods Human cavernosal tissues were obtained from 10 patients undergoing penile surgery. Strips contractility was studied in organ baths. Concentration–response curves to tadalafil were generated on norepinephrine (NE, 1–10 µM)-precontracted strips in the presence of alfuzosin or vehicle. Frequency–response curves (FRC) to electrical field stimulation (EFS, 0–64 Hz, 3 ms, 10 seconds, 300 mA) were generated in the presence of vehicle, alfuzosin, tadalafil, or both drugs combined. EFS (20 Hz, 1 ms, 10 seconds, 300 mM)-induced nitrergic relaxation on NE-precontracted strips was studied in the presence of vehicle, alfuzosin, tadalafil, or both drugs combined. Main Outcome Measures Functional measurement of cavernosal smooth muscle relaxation in the presence of tadalafil and alfuzosin. Results The relaxation induced by tadalafil (10−10 to 10−5 M) on precontracted strips was enhanced by alfuzosin at both 10−8 and 10−7 M. The combination of alfuzosin (3.10−8 M) and tadalafil (10−7 M) was more efficient to inhibit FRC-induced contractions than each compound alone. The combination of tadalafil (10−6 M) and alfuzosin (10−8 M) increased the relaxation induced by EFS and its effect was greater than tadalafil alone. In addition, the combination of tadalafil (10−6 M) and alfuzosin (10−7 M) prolonged EFS-induced relaxation to a greater extent than each compound alone. Conclusions In vitro, the combination of alfuzosin and tadalafil is more efficient than each compound alone to relax adrenergic tone or to enhance nitrergic relaxation of the human corpus cavernosum. Such a combination deserves further investigation in placebo-controlled studies to evaluate its benefit in ED patients who are not sufficiently improved by PDE5 inhibitors.

show abstract

Section: Discussionsupporting

confidence: 79%

Combination of Alfuzosin and Tadalafil Exerts In Vitro an Additive Relaxant Effect on Human Corpus Cavernosum

Oger¹,

Behr‐Roussel²,

Gorny³

et al. 2008

The Journal of Sexual Medicine

View full text Add to dashboard Cite

show abstract

“…[7][8][9][10] Some drugs such as inhibitors of PDE 5 or other vasodilators, which can promote the relaxation of corpus cavernosum smooth muscle, can be potentially used to treat ED. [11][12][13][14][15][16][17][18][19] It has been shown that there are many Chinese traditional herbals that can enhance sexual activity. [20][21][22][23][24] Recently, there is an increasing interest in investigating their effective components.…”

Section: Introductionmentioning

confidence: 99%

Chuanxiongzine relaxes isolated corpus cavernosum strips and raises intracavernous pressure in rabbits

et al. 2009

View full text Add to dashboard Cite

It has been shown that there are many Chinese traditional herbals that can enhance sexual activity. Chuanxiongzine is a vasoactive ingredient that has been isolated and purified from Ligusticum chuanxiong Hort. In previous studies, it has been found that chuanxiongzine was effective in relaxing rabbit corpus cavernosum smooth muscle. We determined the effects of chuanxiongzine on relaxation of isolated corpus cavernosum strips in vitro and on increase of intracavernous pressure (ICP) in vivo in rabbits. Chuanxiongzine caused a concentration-dependent relaxation of phenylephrine precontracted isolated corpus cavernosum strips (EC 50 1.58 Â 10 À4 mol l À1 ), which were endothelium independent and NO independent. However, the guanylyl cyclase inhibitor 1-H-[1,2,4] oxadiazolo [4,3-a] quinoxalin-1-one significantly shifted the chuanxiongzine concentration-response relationship to the right. Although there was no significant difference in the level of cyclic guanosine monophosphate (cGMP) and cyclic adenosine monophosphate (cAMP) in isolated corpus cavernosum strips treated with chuanxiongzine or vehicle, chuanxiongzine caused a significant rise in the level of cGMP and cAMP in isolated corpus cavernosum strips pretreated with the activator of adenylyl cyclase forskolin and the source of NO sodium nitroprusside. In an in vivo study, chuanxiongzine dose-dependently raised ICP after the intracavernous injection of its cumulative doses (0.5, 1, 2 and 5 mg kg À1 ). The ICP increased from baseline to 19.1±3.7, 24.8±2.1, 30.2 ± 4.8 and 39.7 ± 6.1 mm Hg, respectively, and the duration of tumescence ranged from 8.5 ± 2.8 to 22.9 ± 7.3 min. Our results show that chuanxiongzine can relax isolated corpus cavernosum strips of rabbits in vitro and increase ICP of rabbits in vivo, which is neither endothelium dependent nor NO dependent, but may be partly mediated by the inhibition of cAMP phosphodiesterase or cGMP phosphodiesterase.

show abstract

“…These findings are supported by data on the IC 50 values of these drugs in previous studies using isolated smooth muscle. [1314]…”

Section: Discussionmentioning

confidence: 99%

Inhibition by tadalafil of contractility of isolated nonpregnant human myometrium

Sen

Thomas

Das

et al. 2016

Journal of Pharmacology and Pharmacotherapeutics

View full text Add to dashboard Cite

Objective:To investigate the inhibitory effect of tadalafil on the contractility of isolated nonpregnant human myometrium.Materials and Methods:The ability of tadalafil (25, 40, and 63 μM) to inhibit 55 mM KCl-induced contractility of isolated nonpregnant human myometrium was studied. The ability of the ATP-sensitive potassium channel blocker glibenclamide (10 μM) and the calcium-sensitive potassium channel (BKCa) blocker iberiotoxin (100 nM) to reverse the inhibitory effect of 40 μM tadalafil on 55 mM KCl-induced myometrial contractility was also studied.Results:Tadalafil produced a concentration-dependent inhibition of myometrial contractility that was statistically significant at 40 and 63 μM concentrations of tadalafil. The inhibition by tadalafil of myometrial contractility was statistically significantly reversed by the concurrent administration of glibenclamide and iberiotoxin.Conclusions:These results suggest that tadalafil inhibits human myometrial contractility by opening ATP-sensitive potassium channels and BKCa channels. The opening of these channels could have been due to the action of raised intracellular levels of cGMP due to inhibition of PDE-5 by tadalafil. The results suggest that tadalafil could be investigated for use in clinical conditions requiring relaxation of the myometrium.

show abstract

Inhibitors of phosphodiesterase 5 (PDE 5) inhibit the nerve‐induced release of nitric oxide from the rabbit corpus cavernosum

Cited by 15 publications

References 55 publications

Combination of Alfuzosin and Tadalafil Exerts In Vitro an Additive Relaxant Effect on Human Corpus Cavernosum

Combination of Alfuzosin and Tadalafil Exerts In Vitro an Additive Relaxant Effect on Human Corpus Cavernosum

Chuanxiongzine relaxes isolated corpus cavernosum strips and raises intracavernous pressure in rabbits

Inhibition by tadalafil of contractility of isolated nonpregnant human myometrium

Contact Info

Product

Resources

About