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.
Department of Pharmacology, Osaka City University Medical School, Japan.
S
S
Kim
K
K
Ohta
A
A
Hamaguchi
T
T
Omura
K
K
Tominaga
T
T
Yukimura
K
K
Miura
M
M
Tanaka
H
H
Iwao
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