Evaluation of some prostaglandins modulators on rat corpus cavernosum in-vitro: Is relaxation negatively affected by COX-inhibitors?
2019
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 PGE 1 , PGI 2 -analogue and PGE 4 receptor (EP 4 )-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 EP 4 agonist) induced direct relaxation where L902688 showed greater relaxant effect. Sildenafil potentiated the E max 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 A 2 receptor antagonist, 10 −6 M) significantly reduced the potentiatory effect of indomethacin. Only diclofenac succeeded to potentiate sodium nitroprusside (SNP)-induced relaxation. Conclusions EP 4 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 A 2 .
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