| Selected contribution: Effects of aging on cerebrovascular tone and [Ca2+]i. | |
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MedLine Citation:
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PMID: 12819223 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The lower limits of cerebral blood flow autoregulation shift toward high pressures in aged compared with young rats. Intraluminal pressure stimulates contractile mechanisms in cerebral arteries that might, in part, cause an age-dependent shift in autoregulation. The present project tested two hypotheses. First, cerebral artery tone is greater in isolated arteries from aged compared with mature adult rats. Second, aging decreases the modulatory effect of endothelium-derived nitric oxide (NO) and increases vascular smooth muscle Ca2+ sensitivity. Isolated segments of middle cerebral arteries from male 6-, 12-, 20-, and 24-mo-old Fischer 344 rats were cannulated and loaded with fura-2. Diameter and Ca2+ responses to increasing pressure were measured in HEPES, during NO synthase inhibition [NG-nitro-l-arginine methyl ester (l-NAME)], and after removal of the endothelium. Cerebral artery tone (with endothelium) increased with age. Only at the lowest pressure (20 and 40 mmHg) was intracellular Ca2+ concentration ([Ca2+]i) greater in arteries from 24-mo-old rats compared with the other age groups. l-NAME-sensitive constriction increased significantly in arteries from 6- to 20-mo-old rats but declined significantly thereafter in arteries from 24-mo-old rats. [Ca2+]i was less in arteries from 24-mo-old rats compared with the other groups after treatment with l-NAME. Another endothelial-derived factor, insensitive to l-NAME, also decreased significantly with age. For example, at 60 mmHg, the l-NAME-insensitive constriction decreased from 47 +/- 10, 42 +/- 5, 21 +/- 2, and 3 +/- 1 microm in 6-, 12-, 20-, and 24-mo-old rats, respectively. Our data suggest that aging alters cerebral artery tone and [Ca2+]i responses through endothelial-derived NO synthase-sensitive and -insensitive mechanisms. The combined effect of greater cerebral artery tone with less endothelium-dependent modulation may in part contribute to the age-dependent shift in cerebral blood flow autoregulation. |
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Authors:
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Greg G Geary; John N Buchholz |
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Publication Detail:
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Type: In Vitro; Journal Article; Research Support, U.S. Gov't, P.H.S. Date: 2003-06-20 |
Journal Detail:
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Title: Journal of applied physiology (Bethesda, Md. : 1985) Volume: 95 ISSN: 8750-7587 ISO Abbreviation: J. Appl. Physiol. Publication Date: 2003 Oct |
Date Detail:
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Created Date: 2003-09-12 Completed Date: 2004-04-28 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 8502536 Medline TA: J Appl Physiol Country: United States |
Other Details:
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Languages: eng Pagination: 1746-54 Citation Subset: IM |
Affiliation:
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Depts. of Physiology and Pharmacology, School of Medicine, Loma Linda Univ., Loma Linda, CA 92350. ggeary@som.llu.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Aging
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physiology* Animals Body Weight Calcium / metabolism* Cerebrovascular Circulation / drug effects, physiology* Endothelium, Vascular / physiology Enzyme Inhibitors / pharmacology Intracellular Membranes / metabolism* Male NG-Nitroarginine Methyl Ester / pharmacology Nitric Oxide Synthase / antagonists & inhibitors Osmolar Concentration Pressure Rats Rats, Inbred F344 Vasomotor System / drug effects, physiology* |
| Grant Support | |
ID/Acronym/Agency:
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R01-HL-69078-01/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Enzyme Inhibitors; 50903-99-6/NG-Nitroarginine Methyl Ester; 7440-70-2/Calcium; EC 1.14.13.39/Nitric Oxide Synthase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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