The uricosuric effects of dihydropyridine calcium channel blockers in vivo using urate under-excretion animal models

Publication date: April 2018Source: Journal of Pharmacological Sciences, Volume 136, Issue 4Author(s): Takayuki Hori, Motoshi Ouchi, Naoyuki Otani, Masakatsu Nohara, Asuka Morita, Yusuke Otsuka, Promsuk Jutabha, Ikuko Shibasaki, Yasushi Matsushita, Tomoe Fujita, Hirotsugu Fukuda, Naohiko AnzaiAbstractThe purpose of this study was to create novel urate under-excretion animal models using pyrazinamide and to evaluate whether dihydropyridine calcium channel blockers (CCBs) have uricosuric effects in vivo.Adult male ICR mice were treated with pyrazinamide, vehicle (dimethyl sulfoxide: DMSO), or tap water. Thirty minutes later, pyrazinamide-treated mice were given benzbromarone, losartan, nilvadipine, nitrendipine, nifedipine or azelnidipine. Six hours after the second administration, urine (by urinary bladder puncture) and plasma were collected to measure uric acid and creatinine levels, and fractional excretion of uric acid (FEUA) and creatinine clearance (Ccr) were calculated and evaluated. There was no significant difference in the levels of plasma uric acid, plasma creatinine, Ccr, urinary N-acetyl-β-d-glucosaminidase (NAG) and urinary NAG-creatinine ratio between water, DMSO, and pyrazinamide-treated mice. But the FEUA of pyrazinamide-treated mice was significantly lower than water mice. The FEUA was significantly higher in mice taking the dihydropyridine CCBs (nilvadipine, nitrendipine, nifedipine, and high-dose azelnidipine) than in pyrazinamide-treated mice. There was ...
Source: Journal of Pharmacological Sciences - Category: Drugs & Pharmacology Source Type: research