Interaction between nitric oxide and angiotensin II in the endothelium: role in atherosclerosis and hypertension.
BACKGROUND
Although there is overwhelming evidence that hypertension promotes atherosclerosis, the relative contribution and/or interaction of vasoactive and hemodynamic factors remain undefined. Endothelial dysfunction complicates hypertension and is a precursor of atherosclerosis. It is characterized by a reduction in the bioavailability of vasodilators, particularly nitric oxide, and an increase in the activity of vasoconstrictors, including angiotensin (Ang) II and reactive oxygen species (ROS). Nitric oxide antagonizes the vasoconstrictive and pro-atherosclerotic effects of Ang II, whereas Ang II decreases nitric oxide bioavailability by promoting oxidative stress.


OBJECTIVE
The present review will focus on the interaction among nitric oxide, Ang II, and ROS in the endothelium and will examine their role in vascular tone and atherogenesis. In this context, studies from our laboratory will be reviewed demonstrating that salt-sensitive hypertension is a vascular diathesis characterized by a local activation of Ang II and NAD(P)H oxidase-derived ROS in the setting of insufficient nitric oxide. In hypertensive Dahl salt-sensitive rats, a paradigm of human salt-sensitive hypertension, inhibition of Ang II type 1 receptor or NAD(P)H oxidase-derived ROS prevented the development of endothelial dysfunction, upregulation of pro-atherogenic molecules, and vascular ROS generation, independently of blood pressure.


CONCLUSIONS
Salt sensitivity, an independent risk factor for increased cardiovascular morbidity and mortality, affects approximately 50% of hypertensives. Our studies suggest that, in salt-sensitive hypertension, atherogenesis is more closely linked to oxidative stress than to the hemodynamic stress of hypertension. To prevent or arrest atherosclerosis, antihypertensive therapy should aim at restoring the homeostatic balance between vasoactive factors in the vascular wall.
Schulman
Ivonne Hernandez
IH
Nephrology and Hypertension Section, Veterans Affairs Medical Center and Division of Nephrology and Hypertension and Vascular Biology Institute, University of Miami Miller School of Medicine, Miami, Florida 33125, USA.
Zhou
Ming-Sheng
MS
Raij
Leopoldo
L
D000804:Angiotensin II / Q000502:physiology*; D050197:Atherosclerosis / Q000209:etiology*; D004730:Endothelium, Vascular / Q000502:physiology*; D006801:Humans; D006973:Hypertension / Q000209:etiology*; D019255:NADPH Oxidases / Q000502:physiology; D009569:Nitric Oxide / Q000502:physiology*; D052250:Nitric Oxide Synthase Type III / Q000502:physiology; D017382:Reactive Oxygen Species; D051127:Scavenger Receptors, Class E / Q000502:physiology; D013481:Superoxides / Q000378:metabolism
C495137:OLR1 protein, human; D017382:Reactive Oxygen Species; D051127:Scavenger Receptors, Class E; D013481:Superoxides; D000804:Angiotensin II; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; D019255:NADPH Oxidases