Amlodipine alone or combined with terazosin improves lower urinary tract disorder in rat models of benign prostatic hyperplasia or detrusor instability: focus on detrusor overactivity.

Abstract

To investigate the effects of amlodipine, a dihydropyridine calcium-channel blocker, alone or combined with terazosin, on urodynamics in rats with benign prostatic hyperplasia (BPH) and in female rats with detrusor instability (DI). The rat model of BPH was induced by subcutaneous injection of testosterone (0.5 mg per rat for 21 days). The female rat model of DI was induced by partial bladder outlet ligation for 6 weeks. The rats were intragastrically administered with assigned drugs (amlodipine, terazosin or both combined) for 14 days in three experiments. Continuous cystometry was assessed in rats under urethane anaesthesia. Amlodipine at 0.5, 1 and 3 mg/kg significantly decreased the bladder index (BI), threshold pressure (TP), and micturition pressure (MP), and significantly increased intermicturition duration (IMD) in BPH rats. Moreover, amlodipine 0.5 mg/kg plus terazosin 0.4 mg/kg gave the greatest improvements in all urodynamic variables, with a greater decrease in BI, TP, MP and greater increase in IMD than with either of the drugs used alone in BPH and DI rats, and had a similar efficacy to terazosin 1 mg/kg. The combined treatment also gave a greater decrease in nonvoiding bladder contractions in DI rats. Amlodipine alone or combined with terazosin might have the potential to alleviate lower urinary tract symptoms (LUTS). The combined therapy appears to be more suitable for LUTS with predominantly irritative symptoms.