The relaxant effects of electrical field stimulation (EFS) and exogenously applied acetylcholine (ACh) or acidified NaNO2 (a-NaNO2) were investigated in the isolated mouse corpus cavernosum precontracted with phenylephrine hydrochloride (PE). Tetrodotoxin (TTX) blocked the relaxant effects of EFS completely, whereas it had no effect on the responses to ACh or a-NaNO2. Guanethidine and indomethacin failed to affect the electrically or ACh-induced relaxations. Atropine completely blocked the effect of ACh; however, it caused a slight reduction in the relaxation evoked by EFS. NG-Nitro-L-arginine (L-NOARG) reduced the effects of EFS and ACh significantly, but it was ineffective on the relaxations induced by a-NaNO2. The inhibitory action of L-NOARG was partly restored by L-arginine, but not by D-arginine. Methylene blue (MB) and hydroxocobalamin (HC) exhibited significant inhibition on the relaxations evoked by EFS, ACh and a-NaNO2. Hydroquinone (HQ) reduced relaxation due to a-NaNO2, but did not affect that of EFS and ACh. Our findings suggest that EFS-induced relaxations of mouse cavernosal tissue are mediated by a transmitter which probably resembles an organic nitrate.
The purpose of this study was to investigate the effect of gentamicin (100 mg/kg/day, i.p.) treatment on endothelium-dependent and -independent vasodilation in isolated perfused rat kidney, and the effect of amino acid L-arginine (in the drinking water, 2.25 g/l) on renal dysfunction induced by gentamicin. When gentamicin-treated groups were compared with the control group, it was observed that BUN and creatinine levels increased significantly. Also, the relaxant responses induced by acetylcholine, sodium nitroprusside and pinacidil decreased. Histopathological examination indicated acute tubular necrosis in this group. In animals treated with gentamicin together with L-arginine, there was a significant amelioration in the BUN and creatinine levels. The vasodilator responses were similar to those of the control group. Histopathological examination indicated only hydropic degeneration in tubular epithelium of kidney. Co-administration of L-NG-nitroarginine methyl ester (L-NAME) (112.5 mg/l), an inhibitor of nitric oxide synthase, and L-arginine to rats treated with gentamicin did not change the protective effect of L-arginine. In rats receiving L-NAME alone, the level of BUN and creatinine and vasodilation to acetylcholine were not significantly different when compared to those of the control group, while relaxant responses to sodium nitroprusside and pinacidil were increased. These results suggest that gentamicin leads to an impairment in vascular smooth muscle relaxation in addition to acute tubular necrosis in the rat kidney. Supplementation of L-arginine has an important protective effect on gentamicin-induced nephropathy.
We investigated the effects of tempol (4-hydroxy tempo), a membrane-permeable radical scavenger, on gentamicin-induced renal failure in rats. The rats were given gentamicin (100 mg/kg/day, i.p., once a day); and gentamicin (100 mg/kg/day, i.p.) and tempol (3.5, 7 or 14 mg/kg/day, i.p., once a day). At the end of 7 days, the gentamicin group produced the remarkable nephrotoxicity, characterized by a significantly decreased creatinine clearance and increased serum creatinine, blood urea nitrogen (BUN) and daily urine volume when compared with controls. In control the BUN value was 21.2 +/- 0.07 (mg/100 mL); in comparison, it was 96.9 +/- 6.03 in gentamicin group (P < 0.05). Renal histopathologic examination confirmed acute tubular necrosis in this group. In rats treated with gentamicin and tempol a partial improvement in biochemical and histologic parameters was observed. BUN values were 96.9 +/- 6.03 and 36.3 +/- 2.39 in gentamicin, and gentamicin plus tempol (14 mg/kg) treated groups, respectively (P < 0.05). These results suggest that the administration of tempol may have a protective effect on gentamicin-induced nephrotoxicity in rats.
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