Angiotensin II-induced hypertension increases heme oxygenase-1 expression in rat aorta.
BACKGROUND
We investigated the in vivo effects of angiotensin (Ang) II-induced hypertension on heme oxygenase (HO) mRNA and protein expression, activity, and localization in rat aortas.


RESULTS
Infusion of Ang II (0.7 mg x kg(-1) x d(-1)) increased HO-1 mRNA levels to 169+/-31%, 251+/-47%, 339+/-26%, and 370+/-74% of the control level at 1, 3, 5, and 7 days after operation, respectively. The HO-1 protein level at 7 days was markedly upregulated, as was HO activity. Treatment with either losartan (25 mg x kg(-1) x d(-1)) or hydralazine (15 mg x kg(-1) x d(-1)), both of which prevented the Ang II-induced hypertension, blocked HO-1 mRNA upregulation. Norepinephrine infusion (2.8 mg x kg(-1) x d(-1)) produced a degree of hypertension and degree of HO-1 mRNA upregulation similar to those of Ang II infusion, which was again blocked by treatment with hydralazine (382+/-18% and 150+/-30% of the control level, respectively). Immunohistochemical analysis demonstrated that HO-1 is expressed in medial smooth muscle and adventitial cells in normotensive rat aortas, and this is markedly increased in adventitial and endothelial cells in Ang II-induced hypertensive rat aortas. In contrast, HO-2 protein expression was not changed in hypertensive rat aortas.


CONCLUSIONS
These findings indicate that HO-1 is upregulated in hypertensive rat aortas, apparently by mechanisms unique to Ang II and by hemodynamic stress.
Ishizaka
N
N
Department of Medicine, Emory University School of Medicine, Atlanta, Ga 30322, USA.
de León
H
H
Laursen
J B
JB
Fukui
T
T
Wilcox
J N
JN
De Keulenaer
G
G
Griendling
K K
KK
Alexander
R W
RW
D000804:Angiotensin II; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D000975:Antioxidants / Q000378:metabolism; D001011:Aorta / Q000187:drug effects / Q000201:enzymology*; D001713:Biphenyl Compounds / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006419:Heme Oxygenase (Decyclizing) / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D051547:Heme Oxygenase-1; D006973:Hypertension / Q000139:chemically induced*; D007093:Imidazoles / Q000494:pharmacology; D019808:Losartan; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013599:Systole; D013777:Tetrazoles / Q000494:pharmacology; D014662:Vasoconstrictor Agents
D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D000975:Antioxidants; D001713:Biphenyl Compounds; D007093:Imidazoles; D012333:RNA, Messenger; D013777:Tetrazoles; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; D019808:Losartan; D009638:Norepinephrine