Angiotensin II induces cardiac phenotypic modulation and remodeling in vivo in rats.
Cardiac phenotypic modulation and remodeling appear to be involved in the pathophysiology of cardiac hypertrophy and heart failure. We undertook this study to examine whether angiotensin II (Ang II) in vivo, independent of blood pressure, contributes to cardiac phenotypic modulation and remodeling. A low dose (200 ng/kg per minute) of Ang II was continuously infused into rats by osmotic minipump for 24 hours or 3 or 7 days to examine the effects on the expression of cardiac phenotype-related or fibrosis-related genes. This Ang II dose caused a small and gradual increase in blood pressure over 7 days. Left ventricular mRNAs for skeletal alpha-actin, beta-myosin heavy chain, atrial natriuretic polypeptide, and fibronectin were already increased by 6.9-, 1.8-, 4.8-, and 1.5-fold, respectively, after 24 hours of Ang II infusion and by 6.9-, 3.3-, 7.5-, and 2.5-fold, respectively, after 3 days, whereas ventricular alpha-myosin heavy chain and smooth muscle alpha-actin mRNAs were not significantly altered by Ang II infusion. Ventricular transforming growth factor-beta 1 and types I and III collagen mRNA levels did not increase at 24 hours and began to increase by 1.4-, 2.8-, and 2.1-fold, respectively, at 3 days. An increase in left ventricular weight occurred 3 days after Ang II infusion. Treatment with TCV-116 (3 mg/kg per day), a nonpeptide selective angiotensin type 1 receptor antagonist, completely inhibited the above-mentioned Ang II-induced increases in ventricular gene expressions and weight. Hydralazine (10 mg/kg per day), which completely normalized blood pressure, did not block cardiac hypertrophy or increased cardiac gene expressions by Ang II.(ABSTRACT TRUNCATED AT 250 WORDS)
Kim
S
S
Department of Pharmacology, Osaka City University Medical School, Japan.
Ohta
K
K
Hamaguchi
A
A
Yukimura
T
T
Miura
K
K
Iwao
H
H
D000199:Actins / Q000235:genetics; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000235:genetics; D001483:Base Sequence; D001835:Body Weight / Q000187:drug effects; D006332:Cardiomegaly / Q000209:etiology*; D003094:Collagen / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects*; D006321:Heart / Q000187:drug effects*; D008297:Male; D008969:Molecular Sequence Data; D010641:Phenotype; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D016212:Transforming Growth Factor beta / Q000235:genetics
D000199:Actins; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D000804:Angiotensin II; D009320:Atrial Natriuretic Factor; D003094:Collagen