Document Detail


Effect of chronic perinatal hypoxia on the role of rho-kinase in pulmonary artery contraction in newborn lambs.
MedLine Citation:
PMID:  23152110     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Exposure to chronic hypoxia during gestation predisposes infants to neonatal pulmonary hypertension, but the underlying mechanisms remain unclear. Here, we test the hypothesis that moderate continuous hypoxia during gestation causes changes in the rho-kinase pathway that persist in the newborn period, altering vessel tone and responsiveness. Lambs kept at 3,801 m above sea level during gestation and the first 2 wk of life were compared with those with gestation at low altitude. In vitro studies of isolated pulmonary arterial rings found a more forceful contraction in response to KCl and 5-HT in high-altitude compared with low-altitude lambs. There was no difference between the effects of blockers of various pathways of extracellular Ca(2+) entry in low- and high-altitude arteries. In contrast, inhibition of rho-kinase resulted in significantly greater attenuation of 5-HT constriction in high-altitude compared with low-altitude arteries. High-altitude lambs had higher baseline pulmonary artery pressures and greater elevations in pulmonary artery pressure during 15 min of acute hypoxia compared with low-altitude lambs. Despite evidence for an increased role for rho-kinase in high-altitude arteries, in vivo studies found no significant difference between the effects of rho-kinase inhibition on hypoxic pulmonary vasoconstriction in intact high-altitude and low-altitude lambs. We conclude that chronic hypoxia in utero results in increased vasopressor response to both acute hypoxia and serotonin, but that rho-kinase is involved only in the increased response to serotonin.
Authors:
Arlin B Blood; Michael H Terry; Travis A Merritt; Demosthenes G Papamatheakis; Quintin Blood; Jonathon M Ross; Gordon G Power; Lawrence D Longo; Sean M Wilson
Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2012-11-14
Journal Detail:
Title:  American journal of physiology. Regulatory, integrative and comparative physiology     Volume:  304     ISSN:  1522-1490     ISO Abbreviation:  Am. J. Physiol. Regul. Integr. Comp. Physiol.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-01-16     Completed Date:  2013-03-05     Revised Date:  2014-01-23    
Medline Journal Info:
Nlm Unique ID:  100901230     Medline TA:  Am J Physiol Regul Integr Comp Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  R136-46     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / analogs & derivatives,  pharmacology
Altitude
Animals
Animals, Newborn
Arterial Pressure
Calcium Channel Blockers / pharmacology
Chronic Disease
Disease Models, Animal
Dose-Response Relationship, Drug
Fetal Hypoxia / complications*,  enzymology,  physiopathology
Gestational Age
Humans
Infant, Newborn
Persistent Fetal Circulation Syndrome / enzymology,  etiology*,  physiopathology
Protein Kinase Inhibitors / pharmacology
Pulmonary Artery / drug effects,  enzymology*,  physiopathology
Serotonin / pharmacology
Sheep
Time Factors
Vasoconstriction* / drug effects
Vasoconstrictor Agents / pharmacology
rho-Associated Kinases / antagonists & inhibitors,  metabolism*
Grant Support
ID/Acronym/Agency:
5R01 HD-003807-37/HD/NICHD NIH HHS; P01 HD-31226-16/HD/NICHD NIH HHS; P01 HD031226/HD/NICHD NIH HHS; R01 HL095973/HL/NHLBI NIH HHS; R01HL95973/HL/NHLBI NIH HHS; R03 HD-069746/HD/NICHD NIH HHS; R03 HD069746/HD/NICHD NIH HHS
Chemical
Reg. No./Substance:
0/Calcium Channel Blockers; 0/Protein Kinase Inhibitors; 0/Vasoconstrictor Agents; 103745-39-7/fasudil; 333DO1RDJY/Serotonin; 84477-87-2/1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; EC 2.7.11.1/rho-Associated Kinases
Comments/Corrections

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