Document Detail


Cerebral microvascular dilation during hypotension and decreased oxygen tension: a role for nNOS.
MedLine Citation:
PMID:  17630350     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Endothelial (eNOS) and neuronal nitric oxide synthase (nNOS) are implicated as important contributors to cerebral vascular regulation through nitric oxide (NO). However, direct in vivo measurements of NO in the brain have not been used to dissect their relative roles, particularly as related to oxygenation of brain tissue. We found that, in vivo, rat cerebral arterioles had increased NO concentration ([NO]) and diameter at reduced periarteriolar oxygen tension (Po(2)) when either bath oxygen tension or arterial pressure was decreased. Using these protocols with highly selective blockade of nNOS, we tested the hypothesis that brain tissue nNOS could donate NO to the arterioles at rest and during periods of reduced perivascular oxygen tension, such as during hypotension or reduced local availability of oxygen. The decline in periarteriolar Po(2) by bath manipulation increased [NO] and vessel diameter comparable with responses at similarly decreased Po(2) during hypotension. To determine whether the nNOS provided much of the vascular wall NO, nNOS was locally suppressed with the highly selective inhibitor N-(4S)-(4-amino-5-[aminoethyl]aminopentyl)-N'-nitroguanidine. After blockade, resting [NO], Po(2), and diameters decreased, and the increase in [NO] during reduced Po(2) or hypotension was completely absent. However, flow-mediated dilation during occlusion of a collateral arteriole did remain intact after nNOS blockade and the vessel wall [NO] increased to approximately 80% of normal. Therefore, nNOS predominantly increased NO during decreased periarteriolar oxygen tension, such as that during hypotension, but eNOS was the dominant source of NO for flow shear mechanisms.
Authors:
Holly D Bauser-Heaton; H Glenn Bohlen
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2007-07-13
Journal Detail:
Title:  American journal of physiology. Heart and circulatory physiology     Volume:  293     ISSN:  0363-6135     ISO Abbreviation:  Am. J. Physiol. Heart Circ. Physiol.     Publication Date:  2007 Oct 
Date Detail:
Created Date:  2007-10-09     Completed Date:  2007-11-21     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100901228     Medline TA:  Am J Physiol Heart Circ Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  H2193-201     Citation Subset:  IM    
Affiliation:
Department of Cellular and Integrative Physiology, Indiana University Medical School, Indianapolis, Indiana 46202, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Arterioles / physiopathology
Cerebral Cortex* / blood supply,  drug effects,  enzymology,  metabolism
Cerebrovascular Circulation* / drug effects
Disease Models, Animal
Electrodes, Implanted
Endothelium, Vascular / enzymology,  metabolism
Enzyme Inhibitors / pharmacology
Glutamic Acid / metabolism
Guanidines / pharmacology
Hemorrhage / complications,  metabolism,  physiopathology
Hypotension / enzymology,  etiology,  metabolism,  physiopathology*
Male
Microelectrodes
NG-Nitroarginine Methyl Ester / pharmacology
Neurons / drug effects,  enzymology,  metabolism*
Nitric Oxide / metabolism*
Nitric Oxide Synthase / antagonists & inhibitors,  metabolism*
Nitric Oxide Synthase Type III / antagonists & inhibitors,  metabolism
Nitro Compounds / pharmacology
Oxygen / blood*
Rats
Rats, Sprague-Dawley
Vasodilation* / drug effects
Grant Support
ID/Acronym/Agency:
HL-20605/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Enzyme Inhibitors; 0/Guanidines; 0/N-(4-amino-5-(aminoethyl)aminopentyl)-N'-nitroguanidine; 0/Nitro Compounds; 10102-43-9/Nitric Oxide; 50903-99-6/NG-Nitroarginine Methyl Ester; 56-86-0/Glutamic Acid; 7782-44-7/Oxygen; EC 1.14.13.39/Nitric Oxide Synthase; EC 1.14.13.39/Nitric Oxide Synthase Type III; EC 1.14.13.39/Nos1 protein, rat; EC 1.14.13.39/Nos3 protein, rat

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