Angiotensin AT(2) receptor agonist prevents salt-sensitive hypertension in obese Zucker rats

作者：Ali Quaisar; Patel Sanket; Hussain Tahir^*

来源：American Journal of Physiology - Renal Fluid and Electrolyte Physiology, 2015, 308(12): F1379-F1385.

DOI：10.1152/ajprenal.00002.2015

• high-sodium diet
• blood pressure
• obesity
• compound 21

High-sodium intake is a risk factor for the pathogenesis of hypertension, especially in obesity. The present study is designed to investigate whether angiotensin type 2 receptor (AT(2)R) activation with selective agonist C21 prevents high-sodium diet (HSD)-induced hypertension in obese animals. Male obese rats were treated with AT(2)R agonist C21 (1 mg.kg(-1).day(-1), oral) while maintained on either normal-sodium diet (NSD; 0.4%) or HSD (4%) for 2 wk. Radiotelemetric recording showed a time-dependent increase in systolic blood pressure in HSD-fed obese rats, being maximal increase (similar to 27 mmHg) at day 12 of the HSD regimen. C21 treatment completely prevented the increase in blood pressure of HSD-fed rats. Compared with NSD controls, HSD-fed obese rats had greater natriuresis/diuresis and urinary levels of nitrates, and these parameters were further increased by C21 treatment. Also, C21 treatment improved glomerular filtration rate in HSD-fed rats. HSD-fed rats expressed higher level of cortical ANG II, which was reduced to 50% by C21 treatment. HSD feeding and/or C21 treatment had no effects on cortical renin activity and the expression of angiotensin-converting enzyme (ACE) and chymase, which are ANG II-producing enzymes. However, ANG(1-7) concentration and ACE2 activity in the renal cortex were reduced by HSD feeding, and C21 treatment rescued both the parameters. Also, C21 treatment reduced the cortical expression of AT(1)R in HSD-fed rats, but had no effect of AT(2)R expression. We conclude that chronic treatment with the AT(2)R agonist C21 prevents salt-sensitive hypertension in obese rats, and a reduction in the renal ANG II/AT(1)R and enhanced ACE2/ANG(1-7) levels may play a potential role in this phenomenon.

• 出版日期2015-6-15