Heme Oxygenase-1 Induction and Organic Nitrate Therapy: Beneficial Effects on Endothelial Dysfunction, Nitrate Tolerance, and Vascular Oxidative Stress
Figure 2
Effects of HO-1 deficiency versus HO-1 induction on vascular improvement by pentaerithrityl tetranitrate (PETN). (a, b) PETN treatment (75 mg/kg/d for 4d) had no effect on PETN potency (PETN-induced relaxation) in aorta from control mice (HO-1+/+) but caused nitrate tolerance (see area between curves) in aorta from mice with partial HO-1 deficiency (HO-1+/−). In accordance, cardiac mitochondrial ROS formation (L-012 ECL) was increased in PETN-treated HO-1+/− mice. : *versus HO-1+/+/DMSO; #versus HO-1+/−/DMSO. S: solvent; P: PETN-treated. (c, d) Hemin (25 mg/kg i.p.)-triggered HO-1 induction improved high-dose AT-II (1 mg/kg/d for 7d)-induced endothelial dysfunction (ACh-response) in aorta (see area between curves) and NADPH oxidase activity in heart (lucigenin ECL) from control mice (HO-1+/+). : *versus AT-II-treated HO-1+/+/DMSO. (e, f) PETN (75 mg/kg/d for 7d) failed to prevent endothelial dysfunction (ACh-response) induced by low-dose AT-II (0.1 mg/kg/d for 7d) in aorta from HO-1+/− mice (see area between curves). In accordance, PETN did not improve NADPH oxidase activity (2-HE formation by HPLC analysis) in cardiac samples from AT-II-treated HO-1+/− mice. : *versus AT-II-treated HO-1+/−/DMSO. All data are mean ± SEM of aortic rings and hearts from 4-5 animals/group. Modified from [32].
