AT1A receptor‐mediated blood pressure and renal effects of long‐term infusion of a low dose of angiotensin II in C57BL/6J and AT1a receptor‐knockout mice

Abstract

The blood pressure and renal effects of angiotensin II (Ang II) are most commonly studied in rodents either acutely or short‐term infused with high doses of Ang II. Few if any studies have focused on the long‐term effects of a low dose of Ang II on blood pressure and the kidney. In the present study, a low dose of Ang II (400 ng/kg/day, i.p.) was infused continuously for 12 weeks in C57BL/6J (WT) or AT1a receptor‐knockout mice (AT1a‐KO), treated with or without the AT1 receptor antagonist losartan (10 mg/kg/day, p.o.). Ang II caused moderate and time‐dependent increases in systolic blood pressure (SBP) in WT mice (basal: 110 ± 4; Week 4: 120 ± 4; Week 8: 139 ± 3; and Week 12: 134 ± 3 mmHg, p<0.01 vs. basal), which were blocked by losartan. By contrast, Ang II had no effect on SBP in AT1a‐KO mice. 24 h urine and urinary sodium excretion were lower in WT mice infused with Ang II than AT1a‐KO or Ang II‐infused mice treated with losartan (p<0.05).The heart weight to body weight ratio was higher in Ang II‐infused WT mice than in Ang II‐infused mice treated with losartan or AT1a‐KO mice treated with and without Ang II infusion (p<0.01). The kidney weight to body weight ratio is, however, significantly lower in Ang II‐infused WT mice compared to the other groups of mice (p<0.01). Our data strongly suggests that infusion of Ang II, even at an initially non‐pressor dose, for 12 weeks can still elevate blood pressure and cause cardiovascular and renal injury.