Chronic immunoneutralization of brain angiotensin-(1-12) lowers blood pressure in transgenic (mRen2)27 hypertensive rats

Abstract

Angiotensin-(1-12) [ANG-(1-12)] is a newly identified peptide detected in a variety of rat tissues, including the brain. To determine whether brain ANG-(1-12) participates in blood pressure regulation, we treated male adult (mRen2)27 hypertensive rats (24-28 wk of age) with Anti-ANG-(1-12) IgG or Preimmune IgG via an intracerebroventricular cannula for 14 days. Immunoneutralization of brain ANG-(1-12) lowered systolic blood pressure (-43 +/- 8 mmHg on day 3 and -26 +/- 7 mmHg on day 10 from baseline, P < 0.05). Water intake was lower on intracereroventricular day 6 in the Anti-ANG-(1-12) IgG group, accompanied by higher plasma osmolality on day 13, but there were no differences in urine volume, food intake, or body weight during the 2-wk treatment. In Preimmune IgG-treated animals, there were no significant changes in these variables over the 2-wk period. The antihypertensive effects produced by endogenous neutralization of brain ANG-(1-12) suggest that ANG-(1-12) is functionally active in brain pathways regulating blood pressure.

Fig. 1.

Changes from pre-ICV baseline systolic blood pressure (SBP: A) and heart rate (HR: B) in male (mRen2)27 transgenic rats administered artificial cerebrospinal fluid (aCSF), Preimmune IgG or Anti-ANG-(1-12) IgG. A: although aCSF and Preimmune IgG did not lower SBP significantly from pre-ICV baseline values, Anti-ANG-(1-12) IgG treatment lowered SBP throughout the treatment period. B: no consistent changes in HR were observed in the three treatment groups. Values are expressed as means ± SE. pre, preintracerebroventricular (ICV) baseline.*P < 0.05 vs. pre-ICV baseline SBP. #P < 0.05 vs. aCSF and Preimmune IgG on same ICV day.

Fig. 2.

Fluid balance and body weight for rats with chronic intracerebroventricular administration of Anti-ANG-(1-12) IgG or Preimmune IgG. A: water intake. The water intake was lower on ICV day 6 in Anti-ANG-(1-12) IgG group. B: urine volume. C: body weight. D: food intake. Urine volume tended to be lower in rats receiving the Anti-ANG-(1-12) IgG, but this did not attain statistical significance. There were no differences in food intake or body weight during the 2-wk-treatment. E: plasma osmolarity on ICV day 13 was higher in anti-ANG-(1-12) IgG group than Preimmune IgG. Values are expressed as means ± SE. pre, pre-ICV baseline. *P < 0.05 vs Preimmune IgG group.