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The effect of AT1 receptor downregulation in the paraventricular nucleus (PVN) on chronic angiotensin II (AngII)‐salt hypertension in the rat
Author(s) -
King Andrew J,
Haywood JR,
Fink Gregory D,
Northcott Carrie A
Publication year - 2008
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.22.1_supplement.738.16
Subject(s) - endocrinology , medicine , angiotensin ii , receptor , downregulation and upregulation , blood pressure , angiotensin ii receptor type 1 , renin–angiotensin system , chemistry , gene , biochemistry
Previous studies have shown silencing AT1a receptor expression with small hairpin RNA delivered by adenovirus (AT1x) in the PVN attenuated acute systemic AngII‐mediated increases in arterial pressure (AP). In the present study, it was hypothesized that chronic AngII‐salt hypertension would be attenuated after AT1x in PVN. LacZ (a marker gene) or AT1x were injected into the PVN [1 × 10 9 pfu/ml, bilateral (200 nl/site)] of male Sprague Dawley rats (on 2% NaCl diet) instrumented with radiotelemetry transmitters to measure AP and heart rate (HR). Ten days post virus, AngII (150 ng/kg/min) or vehicle was given subcutaneously by minipump for 14 days. Final mean AP was the same in AngII rats treated with AT1x and LacZ (AngII AP: AT1x: 146±11 mmHg, Lac Z: 147±7 mmHg). No differences between groups in HR, weight gain, sodium or water intake were observed. Sympathetic nervous system (SNS) pressor effects were tested using the fall in AP to hexamethonium (30 mg/kg) on infusion day 14. In vehicle rats depressor responses were similar in AT1x (−42±5 mmHg) and Lac Z (−33±4 mmHg) groups. PVN AT1x treatment did not interfere with SNS activation by AngII (AT1x: −93±19 mmHg, LacZ: −80±13 mmHg). Western analyses showed a 34% reduction in AT1a receptors in the PVN (p<0.05). In conclusion, partial downregulation of PVN AT1a receptors did not affect the development of AngII‐salt hypertension or SNS activation in chronic Ang II‐salt hypertension.