Effect of β3 -adrenoceptor Activation on interaction of Renal Adrenoceptors and Angiotensin II Receptors in Aging ApoE-/- mice

To investigate the effect of β 3 -adrenoceptor (β 3 -AR) activation on the interaction of renal adrenoceptor (AR) and angiotensin II receptor (ATR) subtypes in aging apolipoprotein E knockout ( apoE -/- ) mice. 10 C57BL/6J mice served as normal control group (group A) and 50 age-matched apoE -/- mice randomly divided into hyperlipidaemia model group (group B), atorvastatin treatment group ( group C ), low-dose β 3 -AR agonist group (group D), high-dose β 3 -AR agonist group (group E) and β 3 -AR antagonist group (group F) were fed with high fat diet for 38 weeks, treatment in each group was given during the last 12 weeks of the high-fat diet. Then serum non-high density lipoprotein cholesterol (nHDL-C), blood glucose and insulin levels in each group were measured using an automatic biochemical detector. Expression of α 1A -AR, α 1B -AR, α 2A -AR, β 1 -AR, β 2 -AR, β 3 -AR and angiotensin II type 1 (AT 1 R) and type 2 (AT 2 R) receptors in renal tissues were detected by RT-PCR and Western blot, respectively. Results showed that the serum nHDL-C, blood glucose and insulin levels significantly increased in hyperlipidaemia model mice (P<0.01), and the expression of α 1A -AR, AT 1 R and AT 2 R in renal tissues were significantly upregulated (P<0.01), with the expression of α 1B -AR, α 2A -AR, β 1 -AR, β 2 -AR and β 3 -AR downregulated (P<0.01). Compared with group B, nHDL-C, glucose and insulin in aged apoE -/- mice decreased in group D and E (P<0.01). β 3 -AR agonist treatment could down-regulate the expression of α 1A -AR and AT 1 R (P<0.05), and increased α 1B -AR, α 2A -AR, β 1 -AR, β 3 -AR and AT 2 R expression in group D and E (P<0.05), and thus resulted in improved lipid and glucose metabolism in aging hyperlipidaemia ApoE -/- mice, indicating that there are interaction between β 3 - AR and different subtypes of AR, and between β 3 -AR and ATRs, which may play a protective role in renal function injury caused by hyperlipidemia.