Chronic immunoneutralization of brain angiotensin-(1-12) lowers blood pressure in transgenic (mRen2)27 hypertensive rats.
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.
Isa
Katsunori
K
Hypertension and Vascular Research Center, Wake Forest University Health Science, Winston-Salem, North Carolina 27157-1032, USA.
García-Espinosa
Maria Antonia
MA
Arnold
Amy C
AC
Pirro
Nancy T
NT
Tommasi
Ellen N
EN
Ganten
Detlev
D
Chappell
Mark C
MC
Ferrario
Carlos M
CM
Diz
Debra I
DI
D000808:Angiotensinogen; D000809:Angiotensins / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure; D001835:Body Weight; D001921:Brain / Q000378:metabolism*; D004195:Disease Models, Animal; D004326:Drinking; D004435:Eating; D006973:Hypertension / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D007074:Immunoglobulin G / Q000008:administration & dosage*; D015918:Infusion Pumps, Implantable; D008297:Male; D009994:Osmolar Concentration; D010446:Peptide Fragments / Q000276:immunology* / Q000378:metabolism; D051381:Rats; D055647:Rats, Transgenic; D012083:Renin / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D014563:Urodynamics
D000809:Angiotensins; D007074:Immunoglobulin G; D010446:Peptide Fragments; C473112:Ren2 protein, mouse; C515557:proangiotensin-12, rat; D000808:Angiotensinogen; D012083:Renin