The renoprotective effect of shichimotsukokato on hypertension-induced renal dysfunction in spontaneously hypertensive rats

Abstract

Antihypertensive treatment is highly important to prevent the progression of chronic kidney disease. Shichimotsukokato (SKT), a traditional Japanese medicine (i.e., Kampo formula), lowered systolic blood pressure (SBP) in experimental animal models of hypertension. However, its mechanism of action has not been fully elucidated. We investigated the potential renoprotective mechanism of SKT in spontaneously hypertensive rats (SHRs). Ten-week-old SHRs were randomly divided into four groups (six rats per group). In the SHR control group, the SBP increased remarkably during the 8-week experimental period. In the SHRs, SKT extract administered orally at a daily dose of 0.45 or 0.15 g/kg significantly suppressed the increase in SBP to the same extent as telmisartan administered orally at a daily dose of 0.01 g/kg. At the end of the experiment, blood, urine, and kidney cortex tissue samples were examined. The SKT treatment significantly decreased urinary albumin excretion to nearly the same level as the telmisartan treatment. A notable loss of chloride channel 5 (ClC-5), a chloride channel in the proximal renal tubules, occurred in the SHR control group. Thus, we concluded that SKT administration significantly ameliorated this decrease. The mechanism of SKT in reducing urinary albumin excretion is mediated, at least partly, by prevention of the loss of ClC-5 in the renal cortex of SHRs.