Premium
Downregulation of Brain Gα12 Blunts Angiotensin II‐induced Hypertension
Author(s) -
Gao Juan,
Kapusta Daniel R
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.906.16
Subject(s) - chlorisondamine , baroreflex , endocrinology , angiotensin ii , medicine , propranolol , atropine , blood pressure , chemistry , renin–angiotensin system , saline , heart rate
We have shown that down‐regulation of brain Gα12 proteins blunts the pressor response to intracerebroventricular (icv) Angiotensin II (Ang II). Also, Gα12 expression is increased in brains of rats chronically infused s.c. with Ang II. We hypothesize that knock‐down of brain Gα12 will prevent chronic Ang II‐induced hypertension. Rats (n= 5–7/group) received Ang II s.c. (350 ng/kg/min) and were infused i.c.v. with a scrambled (SCR; 50 μg/day) or Gα12 oligodeoxynucleotide (ODN; 50 μg/day). Heart rate (HR) and blood pressure (BP, telemetry) were recorded during the 2 week infusion period. In the end, responses to atropine, propranolol and chlorisondamine were examined and baroreflex activity was analyzed. I.c.v. Gα12 ODN infusion lowered mean BP in Ang II infused rats compared with SCR ODN infusion (14‐ day peak; 133 ± 12 vs 176 ± 11 mmHg, p < 0.05). Compared to the SCR ODN group, Ang II infused rats that received i.c.v. Gα12 ODN showed a significantly (p<0.05) lower basal HR (344 ± 8 vs 397 ± 16 bpm), a greater increase in HR to atropine (Δbpm, 92±12 vs 51±9), and baroreflex sensitivity was improved (HR Gmax, Gα12 ODN, 28.4 ± 8.5 vs SCR ODN, 8.8 ± 2.1 bpm/mmHg). I.c.v. SCR or Gα12 ODN infusion did not alter BP in rats chronically infused s.c. with saline. These data indicate that Ang II impairs the parasympathetic branch of the baroreflex and contributes to the development of hypertension through a central Gα12 pathway. AHA 12GRNT12060613