Both the AT1 receptor antagonist E4177 and the ACE inhibitor cilazapril significantly inhibited vascular remodeling and reduced reactive oxygen species in stroke-prone spontaneously hypertensive rats.
Does an AT1 receptor antagonist or ACE inhibitor improve vascular remodeling and alter ROS-scavenging enzymes in stroke-prone spontaneously hypertensive rats?
AT1 receptor antagonists and ACE inhibitors reduce vascular remodeling and oxidative stress in hypertensive rats partly through the upregulation of Cu/ZnSOD.
Absolute Event Rate: 0.12% vs 0.3%
p-value: p=<0.01
Although angiotensin II type 1 (AT1) receptor antagonists and angiotensin-converting enzyme (ACE) inhibitors are known to reduce both reactive oxygen species (ROS) generated by activated NAD(P)H oxidase and vascular remodeling in hypertension, the effects of AT1 receptor antagonists or ACE inhibitors on ROS-scavenging enzymes remain unclear. We hypothesized that AT1 receptor antagonists or ACE inhibitors may modulate vascular remodeling via superoxide dismutase (SOD) in hypertension. Male stroke-prone spontaneously hypertensive rats (SHRSP) were treated for 6 weeks with a vehicle, an AT1 receptor antagonist (E4177; 30 mg/kg/day), or an ACE inhibitor (cilazapril; 10 mg/kg/day). We evaluated protein expression using immunoblots, determined SOD activities with a spectrophotometric assay, and measured NAD(P)H oxidase activity by a luminescence assay. The two drugs showed equipotent effects on blood pressure, left ventricular hypertrophy and fibrosis, and endothelial NO synthase in the SHRSP hearts. The wall-to-lumen ratio of the intramyocardial arteries and the NAD(P)H oxidase essential subunit p22(phox) and its activity were significantly reduced, whereas Cu/Zu-containing SOD (Cu/ZnSOD) expression and activity were significantly increased in the SHRSP hearts. Furthermore, E4177 reduced vascular remodeling more than did cilazapril not only by reducing p22(phox) expression and NAD(P)H oxidase activity but also by upregulating the Cu/ ZnSOD expression and its activity in the SHRSP hearts. Thus, both the AT1 receptor antagonist and the ACE inhibitor inhibited vascular remodeling and reduced ROS in SHRSP via not only a reduction in NAD(P)H oxidase but also an upregulation of Cu/ZnSOD.
Tanaka et al. (Sat,) conducted a other in Hypertension (Stroke-prone spontaneously hypertensive rats) (n=80). E4177 (AT1 receptor antagonist) or Cilazapril (ACE inhibitor) vs. Vehicle was evaluated on Wall-to-lumen ratio of intramyocardial arteries (p=<0.01). Both the AT1 receptor antagonist E4177 and the ACE inhibitor cilazapril significantly inhibited vascular remodeling and reduced reactive oxygen species in stroke-prone spontaneously hypertensive rats.