Key result
In obese Zucker rats, chronic treatment with candesartan increased renal AT1R but decreased urine AT1R, while high-salt diets markedly increased AT1R excretion compared to low-salt diets.
Why the study?
Does treatment with candesartan, rosiglitazone, or varying salt diets alter renal and urinary AT1R levels in obese Zucker rats?
Does treatment with candesartan, rosiglitazone, or varying salt diets alter renal and urinary AT1R levels in obese Zucker rats?
Urine AT1R correlates with renal AT1R levels only in the untreated state in obese Zucker rats, and its excretion is salt-sensitive, which may have implications for hypertension in metabolic syndrome.
Urine AT1R may track renal expression in metabolic syndrome models; leaves open noninvasive marker utility pending human studies.
Increased renal expression of the angiotensin II, type-1 receptor (AT1R) has been associated with increased blood pressure (BP) and progression of renal disease. We tested whether common medications used to treat hypertension and the metabolic syndrome alter renal AT1R; and whether urine AT1R can be used as a reasonable noninvasive marker of renal levels in the obese Zucker rat, a model for human metabolic syndrome. Immunoblotting revealed that renal and urinary levels of AT1R were significantly higher in obese versus lean rats and correlated (R = 0.62, p < 0.05). Chronic treatment with BP lowering, candesartan, an AT1R antagonist, increased renal levels of AT1R in both lean (282% of lean controls) and obese (178% of obese controls) rats, but decreased urine AT1R levels in obese rats (72% of obese controls). Similarly, chronic treatment with rosiglitazone (RGZ), a peroxisome proliferator activated receptor (subtype gamma) agonist, significantly decreased urine (43% of obese controls) but not renal AT1R (105%) in obese rats. Blood pressure, measured by radiotelemetry, was significantly correlated in untreated and RGZ-treated rats to renal AT1R (R = 0.57, p = 0.0035). Finally, high- (4%) and medium- (0.4%) NaCl diets increased excretion of AT1R in obese rats to approximately 400% of low- (0.04%) NaCl diet. This effect was markedly blunted in lean rats. Overall, we demonstrate increased renal AT1R levels in obese rats. Urine AT1R correlated with renal levels only in the untreated state. Relative salt-sensitivity of AT1R excretion in obese, relative to lean rats, may have implications for both BP and renal disease in the metabolic syndrome.
No takes yet. Share an insight, caveat, or question.
Hu et al. (2009) studied Metabolic syndrome (animal model). Candesartan, rosiglitazone, and varying NaCl diets vs. Lean rats and untreated obese controls was evaluated on Renal and urinary levels of AT1R. In obese Zucker rats, chronic treatment with candesartan increased renal AT1R but decreased urine AT1R, while high-salt diets markedly increased AT1R excretion compared to low-salt diets.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: