AT1 receptor-mediated stimulation by angiotensin II of rat aortic fibronectin gene expression in vivo.
Fibronectin plays an important role in various vascular diseases. A subpressor (200 ng kg-1 min-1) or pressor (1000 ng kg-1 min-1) dose of angiotensin II was continuously infused into rats by osmotic minipump for various times, to investigate the effects on aortic fibronectin gene expression. In rats infused with a subpressor dose of angiotensin II in which blood pressure was normal for 3 days, aortic fibronectin mRNA levels started to increase by 1.4 fold at 12 h and reached the maximal levels (increased by 3.1 fold) at 3 days. Treatment with TCV-116 (3 mg kg-1 day-1), a non-peptide selective AT1 receptor antagonist, completely inhibited the angiotensin II-induced increase in aortic fibronectin mRNA, while hydralazine (10 mg kg-1 day-1) did not block this effect. Similar results were also obtained for a pressor dose of angiotensin II. Thus, angiotensin II directly stimulates aortic fibronectin gene expression in vivo, which is mediated by the AT1 receptor but not by blood pressure.
Kim
S
S
Department of Pharmacology, Osaka City University Medical School, Japan.
Ohta
K
K
Hamaguchi
A
A
Omura
T
T
Tominaga
K
K
Yukimura
T
T
Miura
K
K
Tanaka
M
M
Iwao
H
H
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D005353:Fibronectins / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects*; D008297:Male; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D011945:Receptors, Angiotensin / Q000187:drug effects* / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000235:genetics
D005353:Fibronectins; D012333:RNA, Messenger; D011945:Receptors, Angiotensin; D016212:Transforming Growth Factor beta; D000804:Angiotensin II