The brain renin-angiotensin system modulates angiotensin II-induced hypertension and cardiac hypertrophy.
The potential involvement of the brain renin-angiotensin system in the hypertension induced by subpressor doses of angiotensin II was tested by the use of newly developed transgenic rats with permanent inhibition of brain angiotensinogen synthesis [TGR(ASrAOGEN)]. Basal systolic blood pressure monitored by telemetry was significantly lower in TGR(ASrAOGEN) than in Sprague-Dawley rats (parent strain) (122.5+/-1.5 versus 128.9+/-1.9 mm Hg, respectively; P<0.05). The increase in systolic blood pressure induced by 7 days of chronic angiotensin II infusion was significantly attenuated in TGR(ASrAOGEN) in comparison with control rats (29.8+/-4.2 versus 46. 3+/-2.5 mm Hg, respectively; P<0.005). Moreover, an increase in heart/body weight ratio was evident only in Sprague-Dawley (11.1%) but not in TGR(ASrAOGEN) rats (2.8%). In contrast, mRNA levels of atrial natriuretic peptide (ANP) and collagen III in the left ventricle measured by ribonuclease protection assay were similarly increased in both TGR(ASrAOGEN) (ANP, x2.5; collagen III, x1.8) and Sprague-Dawley rats (ANP, x2.4; collagen III, x2) as a consequence of angiotensin II infusion. Thus, the expression of these genes in the left ventricle seems to be directly stimulated by angiotensin II. However, the hypertensive and hypertrophic effects of subpressor angiotensin II are at least in part mediated by the brain renin-angiotensin system.
Baltatu
O
O
Max-Delbrück Center for Molecular Medicine, Berlin-Buch, Germany. baltatu@mdc-berlin.de
Silva
J A
JA
Ganten
D
D
Bader
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M
D000804:Angiotensin II / Q000494:pharmacology; D000808:Angiotensinogen / Q000235:genetics*; D000818:Animals; D030801:Animals, Genetically Modified; D009320:Atrial Natriuretic Factor / Q000235:genetics; D001794:Blood Pressure / Q000187:drug effects; D001923:Brain Chemistry / Q000502:physiology*; D006332:Cardiomegaly / Q000139:chemically induced / Q000503:physiopathology*; D003094:Collagen / Q000235:genetics; D015870:Gene Expression / Q000502:physiology; D006352:Heart Ventricles / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D006977:Hypertension, Renal / Q000139:chemically induced / Q000503:physiopathology*; D008297:Male; D009206:Myocardium / Q000737:chemistry / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012084:Renin-Angiotensin System / Q000502:physiology*
D012333:RNA, Messenger; D000808:Angiotensinogen; D000804:Angiotensin II; D009320:Atrial Natriuretic Factor; D003094:Collagen