Angiotensin II-induced hypertension increases heme oxygenase-1 expression in rat aorta
Ishizaka, N.; de León, H.; Laursen, J.B.; Fukui, T.; Wilcox, J.N.; De Keulenaer, G.; Griendling, K.K.; Alexander, R.W.
Circulation 96(6): 1923-1929
1997
ISSN/ISBN: 0009-7322 PMID: 9323082 Document Number: 472566
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. Methods and Results: Infusion of Ang II (0.7 mg cntdot kg-1 cntdot 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 cntdot kg-1 cntdot d-1) or hydralazine (15 mg cntdot kg-1 cntdot d-1), both of which prevented the Ang 11-induced hypertension, blocked HO-1 mRNA upregulation. Norepinephrine infusion (2.8 mg cntdot kg-1 cntdot 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.