These findings confirm that only selective 5-HT1A receptor antagonists have favourable effects on the bladder, inducing an increase in bladder capacity with no derangement of bladder contractility.

saline 5 days after catheterization. Effects on isovolumic bladder contractions in anaesthetized rats were also evaluated. RESULTSAll the NSAIDs tested dose-dependently increased BVC; their potency at increasing BVC during infusion of the bladder with acetic acid was similar to that evaluated with saline on cystometry 1 day after catheterization. When a nonselective (naproxen) and a selective (nimesulide) COX-2 inhibitor were tested in rats with bladders infused with saline 5 days after catheterization, their effects on BVC were significantly lower than those evaluated at 1 day. All tested compounds dose-dependently inhibited isovolumic bladder contractions in anaesthetized rats. There was a good correlation between the potency in inhibiting the isovolumic bladder contractions in anaesthetized rats and in increasing BVC during cystometry in conscious rats with the bladder infused with acetic acid. The potency of the compounds in the cystometry model with bladders infused with acetic and in the isovolumic bladder voiding contractions correlated well with COX-2 inhibition, but not COX-1. CONCLUSIONSBoth nonselective and COX-2 selective inhibitors are more active in inhibiting the micturition reflex in rats with bladder overactivity caused by bladder irritation than in normal rats. The potency of the antiinflammatory compounds in inhibiting bladder overactivity induced by chemical or surgical irritation, and their activity in a cystometrographic model practically independent of bladder irritation (isovolumic bladder contractions in anaesthetized rats), was related to the potency as inhibitors of COX-2 isozyme. This suggests that the involvement of prostaglandins in the micturition reflex in rats is mainly mediated by this isozyme. KEYWORDScyclooxygenase inhibitors, isozymes, micturition reflex, bladder capacity, rat OBJECTIVETo investigate the role of cyclooxygenase (COX) isozymes (COX-1 and -2) in the regulation of bladder volume capacity (BVC) in several rat urodynamic models, using a selection of nonsteroidal anti-inflammatory drugs (NSAIDs), some selective for COX-2, correlating the potency of the tested compounds in the urodynamic models and their in vitro potency as inhibitors of COX isozymes, to verify the relative importance of the different isozymes. MATERIALS AND METHODSThe effects of an i.v. administration of several nonselective and selective COX-2 inhibitors (indomethacin, meloxicam, naproxen, aspirin, paracetamol, flurbiprofen, nimesulide, NS-398, celecoxib, rofecoxib and L 745337) on bladder filling and voiding were evaluated in conscious and anaesthetized rats by cystometry. The cystometry was done in conscious rats 1 day after catheter implantation, by filling the bladder with dilute acetic acid (0.2%) or saline, and again with

The aim of this study was to characterize the in-vitro vasoselectivity of lercanidipine (in comparison with lacidipine, amlodipine, nitrendipine and felodipine) by evaluating its functional calcium antagonistic activity on rabbit vascular (aorta) and cardiac tissues (heart ventricle). Although incubation with all the compounds tested elicited a concentration-dependent relaxant effect on vascular tissue precontracted with KCl (80 mM), 50% relaxation was reached at different times for each concentration and drug tested. At 10 nM concentration 50% relaxation was reached after 210 min with lercanidipine, 278 min with amlodipine, 135 min with lacidipine, 75 min with nitrendipine and 70 min with felodipine. The onset of the effect was, therefore, similar for lercanidipine, amlodipine and lacidipine, but faster for nitrendipine and felodipine. Similarly, all the compounds tested concentration-dependently reduced the force of cardiac contraction (negative inotropic activity). In this model, the time needed to reach 50% reduction in contractile force was also concentration-dependent, and the ranking order of the speed of onset of the effect (evaluated as the ratio of the IC50 values (the concentrations inhibiting contraction by 50%) calculated after 1 and 4 h incubation) was lacidipine (3.8) > amlodipine (9.6) > felodipine (39) > lercanidipine (68) = nitrendipine (89). The vasoselectivity, expressed as the ratio of the IC50 values obtained on cardiac and vascular tissue, were (for 4 h incubation) 730, 193, 95, 6 and 3 for lercanidipine, lacidipine, amlodipine, felodipine and nitrendipine, respectively, showing that lercanidipine is the most vasoselective of the calcium-antagonists tested. The results show that lercanidipine reduces the inotropic force of the rabbit heart to a lesser extent than do other calcium antagonists, and that this drug had the best heart/vessel selectivity index among the compounds tested at all the times tested.

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