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In the present study, we investigated the renoprotective effects of long-term treatment with yohimbine, an α2-adrenoceptor inhibitor, in a 5/6 nephrectomy-induced chronic kidney disease (CKD) rat model. Male Sprague–Dawley rats were randomly allocated into the following groups: sham-operated, 5/6-nephrectomized (5/6 Nx), 5/6 Nx + low or high dose of yohimbine (0.3 or 3.0 mg/L in drinking water, respectively), and 5/6 Nx + hydralazine (250 mg/L in drinking water). The 5/6 Nx group presented with renal dysfunction, hypertension, noradrenaline overproduction, and histopathological injuries. Blood pressure decreased in both the yohimbine- and hydralazine-treated groups. Treatment with high dose of yohimbine, but not hydralazine, apparently attenuated urinary protein excretion and noradrenaline concentration of renal venous plasma. Renal fibrosis and upregulated fibrosis-related gene expression were suppressed by high dose of yohimbine. Furthermore, yohimbine, but not hydralazine, treatment ameliorated the urinary concentration ability. These findings suggest that long-term yohimbine treatment can be a useful therapeutic option to prevent the progression of CKD.

Ischemia/reperfusion injury is the most common cause of acute kidney injury. We previously revealed that pre-treatment with yohimbine or JP-1302 attenuated renal ischemia/reperfusion injury by inhibition of α2C-adrenoceptor antagonist. The aim of the present study is to investigate the effects of post-treatment with JP-1302 on renal ischemia/reperfusion injury in rats. Male Sprague Dawley rats were randomly divided into four groups: sham operation, ischemia/reperfusion, pre-treatment with JP-1302 (3.0 mg/kg) and post-treatment with JP-1302 groups. In ischemia/reperfusion injury, renal functional parameters, such as blood urea nitrogen, plasma creatinine and creatinine clearance, deteriorated after reperfusion. Renal venous norepinephrine concentrations, as well as inflammatory molecules in the kidney increased after reperfusion. Both pre- and post-treatment with JP-1302 improved renal dysfunction, tissue damage, renal venous norepinephrine concentrations and inflammatory molecules expression in the kidney. In conclusion, these results suggest that post-treatment with JP-1302 protects on ischemia/reperfusion-induced acute kidney injury by suppressing cytokine upregulation via α2C-adrenoceptors. Keywords: JP-1302, Ischemia/reperfusion, Acute kidney injury, α2C-adrenoceptor, Norepinephrine

Monocytes/macrophages have recently been shown to play a significant role in the pathogenesis of allergic diseases. As the level of soluble CD14 (sCD14) in serum is considered a marker of monocyte/macrophage activation, we measured the levels of sCD14 in allergic asthma and atopic dermatitis (AD), along with acute infectious and inflammatory diseases, to see its clinical relevance. Serum samples were taken from patients with acute infectious and inflammatory diseases, allergic asthma, and atopic dermatitis. sCD14 was measured with our own ELISA system and its level in each disease was compared with normal controls as well as its disease severity. sCD14 was elevated and correlated with C-reactive protein in infectious and inflammatory diseases (n = 26), confirming that it reflects inflammation. sCD14 was also significantly increased both in asthma (n = 94) and adult chronic AD (n = 22). In asthmatic patients, those with higher sCD14 tended to have more severe symptoms, but there was no statistical correlation between sCD14 and severity. In adult chronic AD patients, a correlation between sCD14 and disease severity was observed. However, sCD14 was not elevated in infant AD patients (n = 18) irrespective of severity, suggesting differences in the degree of monocyte/macrophage involvement in the pathogenesis between adult chronic and infant AD. The levels of sCD14 were shown to be upregulated in allergic diseases and might be useful as a marker of monocyte/macrophage involvement in allergic inflammation.