Evaluation of some prostaglandins modulators on rat corpus cavernosum in-vitro: Is relaxation negatively affected by COX-inhibitors? - 16/02/19
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Graphical abstract |
Highlights |
• | EP4-agonist may have an important role in corpus cavernosal relaxation. |
• | Cross-talk between NO/cGMP and PGE1/PGI2 pathway may exist in rat corpus cavernosum. |
• | Selective COX-2 inhibitor have no effect on corpus cavernosal relaxation. |
• | Nonselective COX inhibitors exert a pro-erectile action by potentiating relaxation. |
• | Part of their beneficial effect may be due to inhibition of TXA2 synthesis. |
Abstract |
Introduction |
Prostaglandins (PGs) play an important role in corpus cavernosum relaxation, as evidenced by alprostadil being used as a drug for erectile dysfunction. Reports about the effect of cyclooxygenase (COX) inhibitors on erectile function are highly contradictory.
Aim |
To compare the potential effects of some COX inhibitors with varying COX-1/COX-2 selectivities (indomethacin, ketoprofen and diclofenac) with that of the selective COX-2 inhibitor (DFU) on corpus cavernosal tone in-vitro. The role played by PGE1, PGI2-analogue and PGE4 receptor (EP4)-agonist in controlling corpus cavernosum function and the modulation of their action by sildenafil is also studied.
Methods |
Organ bath experiments were performed using isolated rat corpus cavernosum. Direct relaxations and changes to electric field stimulation (EFS, 2–16 Hz, 60 V, 0.8 ms, 10 s train)-induced relaxation by the effect of the selected drugs were studied. Strips were precontracted using phenylephrine (PE, 10−5 M). Results are expressed as mean ± SEM of 5–9 rats.
Results |
Alprostadil, iloprost and L902688 (selective EP4 agonist) induced direct relaxation where L902688 showed greater relaxant effect. Sildenafil potentiated the Emax of alprostadil and iloprost but not L902688. EFS and acetylcholine (ACh)-induced relaxations were significantly potentiated in presence of indomethacin, ketoprofen and diclofenac (20, 100 μM) but not in presence of selective COX-2 inhibitor (DFU, 1 μM). GR32191B (Thromboxane A2 receptor antagonist, 10−6 M) significantly reduced the potentiatory effect of indomethacin. Only diclofenac succeeded to potentiate sodium nitroprusside (SNP)-induced relaxation.
Conclusions |
EP4 receptors may play an important nitric oxide (NO)/cGMP-independent role in corpus cavernosal relaxation. Nonselective COX inhibitors seem of no harm concerning cavernosal tissue relaxation, possibly because they inhibit the synthesis of the highly contracting mediator thromboxane A2.
Le texte complet de cet article est disponible en PDF.Keywords : Prostaglandins, COX inhibitors, NSAIDs, Sildenafil, Erectile function, Rat corpus cavernosum
Plan
Vol 111
P. 1458-1466 - mars 2019 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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