抄録
It is well known that salt excess accelerates organ injury when the renin-angiotensin system is activated.In the present study,we investigated the mechanisms by which salt excess causes glomerular injury using AT1A receptor overexpression mice,and evaluated the preventive effect of indapamide,a thiazide-like diuretic.Young AT1A receptor overexpression mice and C57BL/6 mice (wild type normal control) were salt-loaded from 8 to 14 weeks old using 1.5% NaCl in drinking water,and kidney specimens were collected.In the indapamide treatment group,10 mg/kg body weight of indapamide was administered concomitantly in the drinking water,and the dose adjusted weekly according to body weight measurements.
Although neither strain of mice exhibited a significant increase in blood pressure after such salt loading during the specified period,increased urinary protein excretion was observed in the AT1A receptor overexpression mice,and indapamide blocked this influence of salt loading.There was a slight increase in the number of glomerular cells due to salt loading in the wild type and a marked increase in the AT1A receptor overexpression mice,which was suppressed by indapamide.Immunostaining of angiotensin II receptors revealed a strong reaction in the glomerular mesangial cells in the latter as opposed to a mild reaction in the former.Furthermore,salt loading induced an increase in collagen IV,a major component of the extracellular matrix (ECM),which was suppressed by indapamide.The present findings suggest that blood pressure and glomerular hypertrophy/ECM deposition are not necessarily connected in young AT1A receptor overexpression mice,and that glomerular injury is accelerated by salt loading.Also indapamide appears to be a promising therapy in the case of a salt excess and an activated renin-angiotensin system.
