Submitted on July 10, 2008
Revised on April 7, 2009
Accepted on April 24, 2009
Chronic Immunoneutralization of Brain Angiotensin-(1-12) Lowers Blood Pressure in Transgenic (mRen2)27 Hypertensive Rats
Katsunori Isa1, Maria Antonia García-Espinosa1, Amy C. Arnold1, Nancy T Pirro, Ellen N. Tommasi, Detlev Ganten2, Mark C. Chappell1, Carlos M Ferrario1, and Debra I. Diz1*
1 Wake Forest University School of Medicine
2 Humboldt University Berlin, Charitsize=
* To whom correspondence should be addressed. E-mail: ddiz{at}wfubmc.edu.
Angiotensin (Ang)-(1-12) is a newly identified peptide detected in a variety of rat tissues including brain. To determine if brain Ang-(1-12) participates in blood pressure regulation, we treated male adult (mRen2)27 hypertensive rats (24 - 28 weeks of age) with Anti-Ang-(1-12)-IgG or Pre-immune IgG via an intracerebroventricular (ICV) cannula for 14 days. Immunoneutralization of brain Ang-(1-12) lowered systolic blood pressure (- 43 ± 8 mm Hg on day 3 and -26 ± 7 mm Hg on day 10 from baseline, p < 0.05). Water intake was lower on ICV 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 week-treatment. In Pre-immune IgG-treated animals, there were no significant changes in these variables over the 2 week 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.
