Exacerbation of Chronic Renovascular Hypertension and Acute Renal Failure in Heme Oxygenase-1–Deficient Mice

Abstract—Heme oxygenase (HO) is a cytoprotective enzyme that degrades heme (a potent oxidant) to generate carbon monoxide (a vasodilatory gas that has anti-inflammatory properties), bilirubin (an antioxidant derived from biliverdin), and iron (sequestered by ferritin). Because of properties of HO and its products, we hypothesized that HO would be important for the regulation of blood pressure and ischemic injury. We studied chronic renovascular hypertension in mice deficient in the inducible isoform of HO (HO-1) using a one kidney–one clip (1K1C) model of disease. Systolic blood pressure was not different between wild-type (HO-1+/+), heterozygous (HO-1+/−), and homozygous null (HO-1−/−) mice at baseline. After 1K1C surgery, HO-1+/+ mice developed hypertension (140±2 mm Hg) and cardiac hypertrophy (cardiac weight index of 5.0±0.2 mg/g) compared with sham-operated HO-1+/+ mice (108±5 mm Hg and 4.1±0.1 mg/g, respectively). However, 1K1C produced more severe hypertension (164±2 mm Hg) and cardiac hypertrophy ...