Document Detail


Central cardiovascular circuits contribute to the neurovascular dysfunction in angiotensin II hypertension.
MedLine Citation:
PMID:  22492044     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Hypertension, a powerful risk factor for stroke and dementia, has damaging effects on the brain and its vessels. In particular, hypertension alters vital cerebrovascular control mechanisms linking neural activity to cerebral perfusion. In experimental models of slow-developing hypertension, free radical signaling in the subfornical organ (SFO), one of the forebrain circumventricular organs, is critical for the hormonal release and sympathetic activation driving the elevation in arterial pressure. However, the contribution of this central mechanism to the cerebrovascular alterations induced by hypertension remains uncertain. We tested the hypothesis that free radical production in the SFO is involved in the alterations in cerebrovascular regulation produced by hypertension. In a mouse model of gradual hypertension induced by chronic administration of subpressor doses of angiotensin II (AngII), suppression of free radicals in the SFO by overexpression of CuZn-superoxide dismutase (CuZnSOD) prevented the alteration in neurovascular coupling and endothelium-dependent responses in somatosensory cortex induced by hypertension. The SFO mediates the dysfunction via two signaling pathways. One involves SFO-dependent activation of the paraventricular hypothalamic nucleus, elevations in plasma vasopressin, upregulation of endothelin-1 in cerebral resistance arterioles and activation of endothelin type A receptors. The other pathway depends on activation of cerebrovascular AngII type 1 (AT1) receptors by AngII. Both pathways mediate vasomotor dysfunction by inducing vascular oxidative stress. The findings implicate for the first time the SFO and its efferent hypothalamic pathways in the cerebrovascular alterations induced by AngII, and identify vasopressin and endothelin-1 as potential therapeutic targets to counteract the devastating effects of hypertension on the brain.
Authors:
Carmen Capone; Giuseppe Faraco; Jeffrey R Peterson; Christal Coleman; Josef Anrather; Teresa A Milner; Virginia M Pickel; Robin L Davisson; Costantino Iadecola
Related Documents :
8063664 - Changes in respiratory muscle activity in ponies when end-expiratory lung volume is inc...
2153474 - Evidence for the existence of inositol tetrakisphosphate in mammalian heart. effect of ...
15138824 - Cardiovascular rhythms in the 0.15-hz band: common origin of identical phenomena in man...
22532844 - The role of sphingosine kinase 1/sphingosine-1-phosphate pathway in the myogenic tone o...
1686784 - Exercise-induced modifications in cardiorespiratory parameters of hypertensive patients...
18067044 - Ambulatory blood pressure and endothelial dysfunction in patients with autosomal domina...
Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  The Journal of neuroscience : the official journal of the Society for Neuroscience     Volume:  32     ISSN:  1529-2401     ISO Abbreviation:  J. Neurosci.     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-04-11     Completed Date:  2012-05-29     Revised Date:  2013-12-06    
Medline Journal Info:
Nlm Unique ID:  8102140     Medline TA:  J Neurosci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4878-86     Citation Subset:  IM    
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Angiotensin II / physiology*,  toxicity*
Animals
Cerebrovascular Circulation / drug effects,  physiology*
Endothelium, Vascular / metabolism,  pathology
Gene Transfer Techniques
Hypertension / chemically induced,  pathology,  physiopathology*
Male
Mice
Mice, Inbred C57BL
Reactive Oxygen Species / metabolism
Receptor, Angiotensin, Type 1 / agonists,  physiology
Subfornical Organ / drug effects,  physiopathology*
Grant Support
ID/Acronym/Agency:
HL96571/HL/NHLBI NIH HHS; HL98351/HL/NHLBI NIH HHS; P01 HL096571-04/HL/NHLBI NIH HHS; R01 HL063887/HL/NHLBI NIH HHS; R01 HL098351/HL/NHLBI NIH HHS; R01 NS073666-01/NS/NINDS NIH HHS; R01 NS073666-02/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Reactive Oxygen Species; 0/Receptor, Angiotensin, Type 1; 11128-99-7/Angiotensin II
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Regulation of MAPK/ERK signaling and photic entrainment of the suprachiasmatic nucleus circadian clo...
Next Document:  G-Protein-Coupled Receptor 30 Mediates Rapid Neuroprotective Effects of Estrogen via Depression of N...