Sildenafil corrects the increased contractility of rat detrusor muscle induced by alprostadil in vitro
Abstract
BACKGROUND: Sildenafil (PDE5-inhibitor) and alprostadil (PGE1) are used in combination clinically for the management of some cases of erectile dysfunction. Despite the roles of prostaglandins (PG) and nitric oxide (NO) pathways in contractility of bladder smooth muscle are frequently studied, the effect of sildenafil/alprostadil combination and the crosstalk between NO/cGMP and PG pathways on bladder activity is not documented.
METHODS: Organ-bath experiments were performed using isolated rat detrusor muscle. Direct and neurogenic contractions were induced using ACh and electric stimulation (EFS, 4Hz, 80V, 1ms), respectively. The contractile responses in absence and presence of the tested drugs at different concentrations were compared. Results are expressed as mean ± SEM (n = 5-7).
RESULTS: Alprostadil (0.01-10 μM) concentration-dependently potentiated ACh (100μM)- and EFS (4 Hz)- induced contraction. Maximum potentiation of ACh-contraction in presence of alprostadil was 40 ± 5%. Sildenafil potentiated ACh-induced contraction at low concentrations (0.01-1 μM), but inhibited it at higher ones (10-100 μM). IBMX (non-selective PDE-inhibitor, 0.01-100μM) and SNP (NO-donor, 1nM-1 mM) produced the same biphasic pattern. The potentiatory phase of sildenafil was inhibited by atropine (0.1μM), L-NAME (non-selective NOS-inhibitor, 100μM), N-PLA (nNOS-inhibitor, 30μM) or MB (nonselective GC-inhibitor, 10μM). In presence of sildenafil (0.1μM), the concentration-response curve of…
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