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

Abstract To investigate the effect of β3-adrenoceptor (β3-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 β3-AR agonist group (group D), high-dose β3-AR agonist group (group E) and β3-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 α1A-AR, α1B-AR, α2A-AR, β1-AR, β2-AR, β3-AR and angiotensin II type 1 (AT1R) and type 2 (AT2R) 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 α1A-AR, AT1R and AT2R in renal tissues were significantly upregulated (P<0.01), with the expression of α1B-AR, α2A-AR, β1-AR, β2-AR and β3-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). β3-AR agonist treatment could down-regulate the expression of α1A-AR and AT1R (P<0.05), and increased α1B-AR, α2A-AR, β1-AR, β3-AR and AT2R 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 β3- AR and different subtypes of AR, and between β3-AR and ATRs, which may play a protective role in renal function injury caused by hyperlipidemia.