Document Detail

Nitric oxide and beta-adrenergic mechanisms modify contractile responses to norepinephrine in ovine fetal and newborn cerebral arteries.
MedLine Citation:
PMID:  7478822     Owner:  NLM     Status:  MEDLINE    
Ovine fetal cerebral arteries exhibit an enhanced contractile response to norepinephrine (NE) compared with newborns and adults. It is possible that beta-adrenergic receptors and/or nitric oxide (NO), a putative endothelium-dependent relaxing factor, differentially modulate cerebrovascular responsiveness to NE as a function of development. The present study evaluated the effect of the beta-adrenoceptor antagonist, propranolol, and the NO synthase inhibitor, NG-nitro-L-arginine methyl ester (LNAME), on the contractile response of isolated middle cerebral artery (MCA) and basilar artery (BA) to NE during fetal development. MCAs isolated from four preterm fetal lambs (105 d of gestation), seven near-term fetal lambs (125-130 d of gestation), and eight newborn lambs (2-7 d of age) were evaluated using organ baths. BAs isolated from the near-term fetal and newborn lambs were also evaluated. Contractile reactivity of MCAs to NE decreased significantly during fetal maturation as manifested by a marked decrease in Fmax (maximal relative contractile force generated) and an increase in EC50 (Fmax = 100 +/- 7, 41 +/- 7, and 28 +/- 8% of KCl contraction; EC50 = 0.14 +/- 0.03, 1.09 +/- 0.36, and 1.07 +/- 0.22 microM for preterm fetus, near-term fetus, and newborn lamb MCAs, respectively, p < or = 0.05). Propranolol treatment (10(-5) M) increased Fmax (2-fold) only for newborn lamb MCAs. Pretreatment with LNAME (10(-4) M) markedly enhanced the contractile response to NE (7-fold decrease in EC50 and 2-fold increase in Fmax, p < 0.05) for near-term fetus MCAs, whereas preterm fetus and newborn lamb MCAs were unaffected by the inhibitor.(ABSTRACT TRUNCATED AT 250 WORDS)
L C Wagerle; W Moliken; P Russo
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Pediatric research     Volume:  38     ISSN:  0031-3998     ISO Abbreviation:  Pediatr. Res.     Publication Date:  1995 Aug 
Date Detail:
Created Date:  1995-12-15     Completed Date:  1995-12-15     Revised Date:  2005-11-17    
Medline Journal Info:
Nlm Unique ID:  0100714     Medline TA:  Pediatr Res     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  237-42     Citation Subset:  IM    
Department of Surgery, Temple University School of Medicine, Philadelphia, Pennsylvania 19102, USA.
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MeSH Terms
Adrenergic beta-Antagonists / pharmacology
Aging / physiology*
Animals, Newborn
Arginine / analogs & derivatives,  pharmacology
Cerebral Arteries / drug effects*,  embryology
Embryonic and Fetal Development / drug effects
Enzyme Inhibitors / pharmacology
NG-Nitroarginine Methyl Ester
Nitric Oxide / pharmacology*
Nitric Oxide Synthase / antagonists & inhibitors,  physiology*
Norepinephrine / pharmacology*
Propranolol / pharmacology
Receptors, Adrenergic, beta / physiology*
Vasoconstrictor Agents / pharmacology*
Vasodilator Agents / pharmacology
Reg. No./Substance:
0/Adrenergic beta-Antagonists; 0/Enzyme Inhibitors; 0/Receptors, Adrenergic, beta; 0/Vasoconstrictor Agents; 0/Vasodilator Agents; 10102-43-9/Nitric Oxide; 50903-99-6/NG-Nitroarginine Methyl Ester; 51-41-2/Norepinephrine; 525-66-6/Propranolol; 74-79-3/Arginine; EC Oxide Synthase

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