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Effects of angiotensin II on the cerebral circulation: role of oxidative stress.

De Silva TM, Faraci FM - Front Physiol (2013)

Bottom Line: Angiotensin II (Ang II) is the main effector peptide of the renin-angiotensin system (RAS) and plays a critical role in promoting oxidative stress in the vasculature.Importantly, many of the aforementioned effects have been shown to be dependent on NADPH oxidases.This review will focus on our current understanding of the contribution of Ang II and NADPH oxidases to oxidative stress in the cerebral circulation.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine, Cardiovascular Center, The University of Iowa Carver College of Medicine Iowa City, IA, USA.

ABSTRACT
Oxidative stress has emerged as a key component of many diseases that affect the vasculature. Oxidative stress is characterized as a cellular environment where the generation of oxidant molecules overwhelms endogenous anti-oxidant defense mechanisms. NADPH oxidases are a family of enzymes whose primary purpose is generation of reactive oxygen species (oxidant molecules) and therefore are likely to be key contributors to oxidative stress. Hypertension is associated with oxidative stress in the vasculature and is a major risk factor for stroke and cognitive abnormalities. Angiotensin II (Ang II) is the main effector peptide of the renin-angiotensin system (RAS) and plays a critical role in promoting oxidative stress in the vasculature. In the cerebral circulation, Ang II has been implicated in reactive oxygen species generation, alterations to vasomotor function, impaired neurovascular coupling, inflammation, and vascular remodeling. Furthermore, studies in humans have shown that cerebral blood flow is altered during hypertension and therapeutically targeting the RAS improves cerebral blood flow. Importantly, many of the aforementioned effects have been shown to be dependent on NADPH oxidases. Thus, Ang II, NADPH oxidases and oxidative stress are likely to play key roles in the pathogenesis of hypertension and associated cerebrovascular disease. This review will focus on our current understanding of the contribution of Ang II and NADPH oxidases to oxidative stress in the cerebral circulation.

No MeSH data available.


Related in: MedlinePlus

Angiotensin II (Ang II) promotes oxidative stress in the vasculature via stimulation of AT1 receptors and subsequent activation of NADPH oxidases. Oxidative stress contributes to blood-brain barrier (BBB) dysfunction, impairment of vasodilation and neurovascular coupling, and promotes inward vascular remodeling and inflammation. Overall, these effects contribute to reductions in cerebral blood flow, which can lead to dementia and increased susceptibility for stroke and lessen recovery following stroke or other forms of brain injury.
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Figure 2: Angiotensin II (Ang II) promotes oxidative stress in the vasculature via stimulation of AT1 receptors and subsequent activation of NADPH oxidases. Oxidative stress contributes to blood-brain barrier (BBB) dysfunction, impairment of vasodilation and neurovascular coupling, and promotes inward vascular remodeling and inflammation. Overall, these effects contribute to reductions in cerebral blood flow, which can lead to dementia and increased susceptibility for stroke and lessen recovery following stroke or other forms of brain injury.

Mentions: In addition to direct effects on vasomotor tone, Ang II impairs endothelium-dependent vasodilation by reducing the bioavailability of NO· and potentially by interfering with other endothelium-dependent mechanisms. This effect is intimately linked with the increased production of ROS (mainly O2·−) in response to Ang II and resulting impairment of NO·-mediated signaling (Figure 2). Consistent with this concept, numerous studies indicate that Ang II has deleterious effects on cerebrovascular function. Indeed, in multiple models (both acute and chronic administration) (Gerzanich et al., 2003; Faraci et al., 2006; Kitayama et al., 2006; Chrissobolis and Faraci, 2010; Chrissobolis et al., 2012), Ang II impairs endothelium-dependent vasodilation cerebral blood vessels. Treatment with scavengers of O2·− improved endothelial function, thus indicating that oxidative stress played a key role in producing this dysfunction (Faraci et al., 2006; Kitayama et al., 2006; Chrissobolis and Faraci, 2010). A recent study has provided, further evidence supporting a role for NADPH oxidase-derived ROS in causing oxidative stress in response to Ang II treatment. Specifically, 7-days Ang II treatment did not result in impaired endothelium-dependent vasodilatation in arteries from Nox2 deficient mice (Chrissobolis et al., 2012). This same study reported a small role for the Nox1-containing NADPH oxidase in this model of Ang II-induced dysfunction (Chrissobolis et al., 2012). Further studies will be needed to better define the role of this isoform of NADPH oxidase as well as Nox4- and Nox5-containing NADPH oxidase in hypertension as well as other disease states.


Effects of angiotensin II on the cerebral circulation: role of oxidative stress.

De Silva TM, Faraci FM - Front Physiol (2013)

Angiotensin II (Ang II) promotes oxidative stress in the vasculature via stimulation of AT1 receptors and subsequent activation of NADPH oxidases. Oxidative stress contributes to blood-brain barrier (BBB) dysfunction, impairment of vasodilation and neurovascular coupling, and promotes inward vascular remodeling and inflammation. Overall, these effects contribute to reductions in cerebral blood flow, which can lead to dementia and increased susceptibility for stroke and lessen recovery following stroke or other forms of brain injury.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3539653&req=5

Figure 2: Angiotensin II (Ang II) promotes oxidative stress in the vasculature via stimulation of AT1 receptors and subsequent activation of NADPH oxidases. Oxidative stress contributes to blood-brain barrier (BBB) dysfunction, impairment of vasodilation and neurovascular coupling, and promotes inward vascular remodeling and inflammation. Overall, these effects contribute to reductions in cerebral blood flow, which can lead to dementia and increased susceptibility for stroke and lessen recovery following stroke or other forms of brain injury.
Mentions: In addition to direct effects on vasomotor tone, Ang II impairs endothelium-dependent vasodilation by reducing the bioavailability of NO· and potentially by interfering with other endothelium-dependent mechanisms. This effect is intimately linked with the increased production of ROS (mainly O2·−) in response to Ang II and resulting impairment of NO·-mediated signaling (Figure 2). Consistent with this concept, numerous studies indicate that Ang II has deleterious effects on cerebrovascular function. Indeed, in multiple models (both acute and chronic administration) (Gerzanich et al., 2003; Faraci et al., 2006; Kitayama et al., 2006; Chrissobolis and Faraci, 2010; Chrissobolis et al., 2012), Ang II impairs endothelium-dependent vasodilation cerebral blood vessels. Treatment with scavengers of O2·− improved endothelial function, thus indicating that oxidative stress played a key role in producing this dysfunction (Faraci et al., 2006; Kitayama et al., 2006; Chrissobolis and Faraci, 2010). A recent study has provided, further evidence supporting a role for NADPH oxidase-derived ROS in causing oxidative stress in response to Ang II treatment. Specifically, 7-days Ang II treatment did not result in impaired endothelium-dependent vasodilatation in arteries from Nox2 deficient mice (Chrissobolis et al., 2012). This same study reported a small role for the Nox1-containing NADPH oxidase in this model of Ang II-induced dysfunction (Chrissobolis et al., 2012). Further studies will be needed to better define the role of this isoform of NADPH oxidase as well as Nox4- and Nox5-containing NADPH oxidase in hypertension as well as other disease states.

Bottom Line: Angiotensin II (Ang II) is the main effector peptide of the renin-angiotensin system (RAS) and plays a critical role in promoting oxidative stress in the vasculature.Importantly, many of the aforementioned effects have been shown to be dependent on NADPH oxidases.This review will focus on our current understanding of the contribution of Ang II and NADPH oxidases to oxidative stress in the cerebral circulation.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine, Cardiovascular Center, The University of Iowa Carver College of Medicine Iowa City, IA, USA.

ABSTRACT
Oxidative stress has emerged as a key component of many diseases that affect the vasculature. Oxidative stress is characterized as a cellular environment where the generation of oxidant molecules overwhelms endogenous anti-oxidant defense mechanisms. NADPH oxidases are a family of enzymes whose primary purpose is generation of reactive oxygen species (oxidant molecules) and therefore are likely to be key contributors to oxidative stress. Hypertension is associated with oxidative stress in the vasculature and is a major risk factor for stroke and cognitive abnormalities. Angiotensin II (Ang II) is the main effector peptide of the renin-angiotensin system (RAS) and plays a critical role in promoting oxidative stress in the vasculature. In the cerebral circulation, Ang II has been implicated in reactive oxygen species generation, alterations to vasomotor function, impaired neurovascular coupling, inflammation, and vascular remodeling. Furthermore, studies in humans have shown that cerebral blood flow is altered during hypertension and therapeutically targeting the RAS improves cerebral blood flow. Importantly, many of the aforementioned effects have been shown to be dependent on NADPH oxidases. Thus, Ang II, NADPH oxidases and oxidative stress are likely to play key roles in the pathogenesis of hypertension and associated cerebrovascular disease. This review will focus on our current understanding of the contribution of Ang II and NADPH oxidases to oxidative stress in the cerebral circulation.

No MeSH data available.


Related in: MedlinePlus