Losartan ameliorates renal injury, hypertension, and adipocytokine imbalance in 5/6 nephrectomized rats.

ABSTRACT

The mechanisms underlying insulin sensitivity and fat tissue distribution in chronic renal insufficiency remain unclear. Previous studies have shown the benefits of angiotensin II receptor blockers on moderately nourished to well-nourished patients with the metabolic syndrome. The current study explored the effect of losartan, the first selective angiotensin II receptor blocker, on insulin sensitivity and visceral fat tissue distribution in a 5/6 nephrectomized (N) rat model and investigated the expression of adipose tissue adipocytokines. Male Sprague-Dawley rats (200 g to 250 g) were subjected to 5/6 nephrectomy, and the adipocytes isolated from the visceral fat tissues were then studied. Results showed that desmin expression was significantly suppressed and systolic blood pressure was successfully normalized in the losartan-administered (NA) group. The weight of the visceral fat pad remarkably decreased in the N and NA groups (100 mg/500 ml drinking water) compared with the control group. The weight did not decrease further in the NA group compared with the N group. Insulin resistance was more remarkable in the N group compared with the control and NA groups. Moreover, the adipose tissue expression of adiponectin and leptin was downregulated whereas that of resistin was upregulated in the N group compared with the control group. However, the adiponectin, leptin, and resistin adipose tissue expression returned to their basal values in the NA group. These findings indicated that losartan administration ameliorated renal injury, systolic blood pressure, and adipocytokine imbalance of the adipose tissue in chronic renal insufficiency. Insulin sensitivity was not improved.