Factors derived from adrenals are required for activation of cardiac gene expression in angiotensin II-induced hypertension.
The mechanisms mediating the activation of cardiac gene expression during pressure overload are not fully understood. We examined whether angiotensin II-induced activation of ventricular gene expression is related to blood pressure and ventricular mass or requires other factors by infusing angiotensin II in sham-operated and adrenalectomized rats. In sham-operated rats, angiotensin II (33 microg/kg x h, sc) produced a significant increase in mean arterial pressure (measured by telemetry) within 3 h. Mean arterial pressure (up to 45 h) and the increase in left ventricular hypertrophy in adrenalectomized rats during angiotensin II infusion were similar to those in sham-operated rats. Angiotensin II produced 3.6-fold (P < 0.01) and 20.4-fold (P < 0.001) increases in ventricular atrial natriuretic peptide mRNA levels at 12 and 72 h, respectively. Angiotensin II infusion for 12 h also significantly increased the ventricular mRNA levels of B-type natriuretic peptide (5.2-fold) and adrenomedullin (1.4-fold). Adrenalectomy either abolished (atrial natriuretic peptide and adrenomedullin) or blunted (B-type natriuretic peptide) the early activation of ventricular gene expression by angiotensin II. The baseline synthesis of atrial natriuretic peptide, B-type natriuretic peptide, and adrenomedullin in the ventricle remained unchanged in adrenalectomized rats. In conclusion, our results indicate that factors derived from the adrenals are required for angiotensin II-induced early activation of cardiac gene expression.
Földes
G
G
First Department of Internal Medicine, Semmelweiss University, Budapest, Hungary.
Suo
M
M
Szokodi
I
I
Lakó-Futó
Z
Z
deChâtel
R
R
Vuolteenaho
O
O
Huttunen
P
P
Ruskoaho
H
H
Tóth
M
M
D000311:Adrenal Glands / Q000503:physiopathology*; D000804:Angiotensin II; D000818:Animals; D005786:Gene Expression Regulation; D006321:Heart / Q000503:physiopathology*; D006973:Hypertension / Q000235:genetics / Q000503:physiopathology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D000804:Angiotensin II