Document Detail


The cerebrovascular dysfunction induced by slow pressor doses of angiotensin II precedes the development of hypertension.
MedLine Citation:
PMID:  20971763     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Hypertension alters cerebrovascular regulation and increases the brain's susceptibility to stroke and dementia. We investigated the temporal relationships between the arterial pressure (AP) elevation induced by "slow pressor" angiotensin II (ANG II) infusion, which recapitulates key features of human hypertension, and the resulting cerebrovascular dysfunction. Minipumps delivering saline or ANG II for 14 days were implanted subcutaneously in C57BL/6 mice (n = 5/group). Cerebral blood flow was assessed by laser-Doppler flowmetry in anesthetized mice equipped with a cranial window. With ANG II (600 ng · kg(-1) · min(-1)), AP started to rise after 9 days (P < 0.05 vs. saline), remained elevated at 11-17 days, and returned to baseline at 21 days (P > 0.05). ANG II attenuated the cerebral blood flow increase induced by neural activity (whisker stimulation) or endothelium-dependent vasodilators, an effect observed before the AP elevation (7 days), as well as after the hypertension subsided (21 days). Nonpressor doses of ANG II (200 ng · kg(-1) · min(-1)) induced cerebrovascular dysfunction and oxidative stress without elevating AP (P > 0.05 vs. saline), whereas phenylephrine elevated AP without inducing cerebrovascular effects. ANG II (600 ng · kg(-1) · min(-1)) augmented neocortical reactive oxygen species (ROS) with a time course similar to that of the cerebrovascular dysfunction. Neocortical application of the ROS scavenger manganic(I-II)meso-tetrakis(4-benzoic acid)porphyrin or the NADPH oxidase peptide inhibitor gp91ds-tat attenuated ROS and cerebrovascular dysfunction. We conclude that the alterations in neurovascular regulation induced by slow pressor ANG II develop before hypertension and persist beyond AP normalization but are not permanent. The findings unveil a striking susceptibility of cerebrovascular function to the deleterious effects of ANG II and raise the possibility that cerebrovascular dysregulation precedes the elevation in AP also in patients with ANG II-dependent hypertension.
Authors:
Carmen Capone; Giuseppe Faraco; Laibaik Park; Xian Cao; Robin L Davisson; Costantino Iadecola
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2010-10-22
Journal Detail:
Title:  American journal of physiology. Heart and circulatory physiology     Volume:  300     ISSN:  1522-1539     ISO Abbreviation:  Am. J. Physiol. Heart Circ. Physiol.     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2011-01-04     Completed Date:  2011-01-28     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  100901228     Medline TA:  Am J Physiol Heart Circ Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  H397-407     Citation Subset:  IM    
Affiliation:
Division of Neurobiology, Department of Neurology and Neuroscience, Weill Cornell Medical College, New York, New York, USA.
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MeSH Terms
Descriptor/Qualifier:
Analysis of Variance
Angiotensin II / administration & dosage*,  metabolism
Animals
Blood Pressure / drug effects*
Cerebrovascular Circulation / drug effects*,  physiology
Electrophysiology
Evoked Potentials / drug effects
Hypertension / chemically induced*,  metabolism
Immunohistochemistry
Infusion Pumps
Laser-Doppler Flowmetry
Mice
Mice, Inbred C57BL
Oxidative Stress / drug effects
Reactive Oxygen Species / metabolism
Telemetry
Time Factors
Vasoconstrictor Agents / administration & dosage,  metabolism
Vibrissae / physiology
Grant Support
ID/Acronym/Agency:
HL-96571/HL/NHLBI NIH HHS; R01 HL063887-11/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Reactive Oxygen Species; 0/Vasoconstrictor Agents; 11128-99-7/Angiotensin II
Comments/Corrections

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