Document Detail


Eucapnic intermittent hypoxia augments endothelin-1 vasoconstriction in rats: role of PKCdelta.
MedLine Citation:
PMID:  18083893     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We reported previously that simulating sleep apnea by exposing rats to eucapnic intermittent hypoxia (E-IH) causes endothelin-dependent hypertension and increases constrictor sensitivity to endothelin-1 (ET-1). In addition, augmented ET-1-induced constriction in small mesenteric arteries (sMA) is mediated by increased Ca(2+) sensitization independent of Rho-associated kinase. We hypothesized that exposing rats to E-IH augments ET-1-mediated vasoconstriction by increasing protein kinase C (PKC)-dependent Ca(2+) sensitization. In sMA, the nonselective PKC inhibitor GF-109203x (3 microM) significantly inhibited ET-1-stimulated constriction in E-IH arteries but did not affect ET-1-stimulated constriction in sham arteries. Phospholipase C inhibitor U-73122 (1 microM) also inhibited constriction by ET-1 in E-IH but not sham sMA. In contrast, the classical PKC (cPKC) inhibitor Gö-6976 (1 microM) had no effect on ET-1-mediated vasoconstriction in either group, but a PKCdelta-selective inhibitor (rottlerin, 3 microM) significantly decreased ET-1-mediated constriction in E-IH but not in sham sMA. ET-1 increased PKCdelta phosphorylation in E-IH but not sham sMA. In contrast, ET-1 constriction in thoracic aorta from both sham and E-IH rats was inhibited by Gö-6976 but not by rottlerin. These observations support our hypothesis that E-IH exposure significantly increases ET-1-mediated constriction of sMA through PKCdelta activation and modestly augments ET-1 contraction in thoracic aorta through activation of one or more cPKC isoforms. Therefore, upregulation of a PKC pathway may contribute to elevated ET-1-dependent vascular resistance in this model of hypertension.
Authors:
Kyan J Allahdadi; Laura C Duling; Benjimen R Walker; Nancy L Kanagy
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, N.I.H., Extramural     Date:  2007-12-14
Journal Detail:
Title:  American journal of physiology. Heart and circulatory physiology     Volume:  294     ISSN:  0363-6135     ISO Abbreviation:  Am. J. Physiol. Heart Circ. Physiol.     Publication Date:  2008 Feb 
Date Detail:
Created Date:  2008-02-12     Completed Date:  2008-03-31     Revised Date:  2014-09-18    
Medline Journal Info:
Nlm Unique ID:  100901228     Medline TA:  Am J Physiol Heart Circ Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  H920-7     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Anoxia / physiopathology*
Aorta, Thoracic / drug effects,  physiology
Blood Pressure / drug effects
Body Weight / drug effects
Carbon Dioxide / physiology*
Diglycerides / metabolism
Endothelin-1 / pharmacology*
Endothelium, Vascular / drug effects
Enzyme Inhibitors / pharmacology
Male
Mesenteric Arteries / physiology
Muscle Contraction / drug effects
Muscle, Smooth, Vascular / drug effects
Protein Kinase C-delta / antagonists & inhibitors,  physiology*
Rats
Rats, Sprague-Dawley
Type C Phospholipases / antagonists & inhibitors
Vasoconstriction / drug effects*,  physiology
Grant Support
ID/Acronym/Agency:
HL-58124/HL/NHLBI NIH HHS; HL-63207/HL/NHLBI NIH HHS; HL-82799/HL/NHLBI NIH HHS; R01 HL082799/HL/NHLBI NIH HHS; R01 HL082799-01A2/HL/NHLBI NIH HHS; RD-83186001/RD/ORD VA
Chemical
Reg. No./Substance:
0/Diglycerides; 0/Endothelin-1; 0/Enzyme Inhibitors; 142M471B3J/Carbon Dioxide; EC 2.7.11.13/Protein Kinase C-delta; EC 3.1.4.-/Type C Phospholipases
Comments/Corrections

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


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