Angiotensin II–Induced Hypertension Increases Heme Oxygenase-1 Expression in Rat Aorta

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Abstract
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 · kg −1 · 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 · kg −1 · d −1 ) or hydralazine (15 mg · kg −1 · d −1 ), both of which prevented the Ang II–induced hypertension, blocked HO-1 mRNA upregulation. Norepinephrine infusion (2.8 mg · kg −1 · 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.

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