Document Detail


Expression of prostaglandin H2-mediated mechanism of vascular contraction in hypertensive rats. Relation to lipoxygenase and prostacyclin synthase activities.
MedLine Citation:
PMID:  8293559     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We tested the hypothesis that a prostanoid-mediated mechanism of vascular contraction is expressed in rats with aortic coarctation-induced hypertension. Rings of descending thoracic aorta taken from normotensive and hypertensive rats were contrasted in terms of constrictor responsiveness to arachidonic acid (AA), AA-induced release of eicosanoids, and ability to convert exogenous prostaglandin (PG) H2 to PGI2. AA (10(-8) to 10(-5) mol/L) increased isometric tension in aortic rings (bathed in Krebs' bicarbonate buffer) of hypertensive but not normotensive rats. AA (10(-5) mol/L) also elicited the release of PGI2, PGE2, thromboxane (TX) A2, and monohydroxyeicosatetraenoic acids (HETEs); this release from the aortic rings of hypertensive rats exceeded the corresponding release from the aortic rings of normotensive rats. However, the rate of conversion of exogenous PGH2 to PGI2 by aortic rings of hypertensive rats was < 50% the rate of conversion by aortic rings of normotensive rats. The constrictor effect of AA in aortic rings of hypertensive rats was abolished by an inhibitor of cyclooxygenase (indomethacin, 10 mumol/L) and a blocker of TXA2-PGH2 receptors (SQ29548, 1 mumol/L) but was not affected by an inhibitor of TXA2 synthesis (CGS13080, 10 mumol/L), suggesting mediation by PGH2. The lipoxygenase inhibitor baicalein (75 mumol/L) also attenuated the constrictor effect of AA in aortic rings of hypertensive rats while decreasing the associated release of HETEs and correcting the impairment in the conversion of PGH2 to PGI2.(ABSTRACT TRUNCATED AT 250 WORDS)
Authors:
L Lin; M Balazy; P J Pagano; A Nasjletti
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Circulation research     Volume:  74     ISSN:  0009-7330     ISO Abbreviation:  Circ. Res.     Publication Date:  1994 Feb 
Date Detail:
Created Date:  1994-02-28     Completed Date:  1994-02-28     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0047103     Medline TA:  Circ Res     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  197-205     Citation Subset:  IM    
Affiliation:
Department of Pharmacology, New York Medical College, Valhalla 10595.
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MeSH Terms
Descriptor/Qualifier:
Animals
Aortic Coarctation / complications
Arachidonic Acid / pharmacology
Cyclooxygenase Inhibitors / pharmacology
Cytochrome P-450 Enzyme System / metabolism*
Hypertension / enzymology*,  etiology,  physiopathology*
Intramolecular Oxidoreductases*
Isomerases / metabolism*
Isometric Contraction / drug effects
Lipoxygenase / metabolism*
Lipoxygenase Inhibitors / pharmacology
Male
Prostaglandin H2
Prostaglandins H / physiology*
Rats
Rats, Sprague-Dawley
Receptors, Prostaglandin / antagonists & inhibitors
Receptors, Thromboxane / antagonists & inhibitors
Receptors, Thromboxane A2, Prostaglandin H2
Thromboxane-A Synthase / antagonists & inhibitors
Vasoconstriction / drug effects,  physiology*
Grant Support
ID/Acronym/Agency:
5PO1 HL-34300/HL/NHLBI NIH HHS; HL-18579/HL/NHLBI NIH HHS; HL-36670/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Cyclooxygenase Inhibitors; 0/Lipoxygenase Inhibitors; 0/Prostaglandins H; 0/Receptors, Prostaglandin; 0/Receptors, Thromboxane; 0/Receptors, Thromboxane A2, Prostaglandin H2; 42935-17-1/Prostaglandin H2; 506-32-1/Arachidonic Acid; 9035-51-2/Cytochrome P-450 Enzyme System; EC 1.13.11.12/Lipoxygenase; EC 5.-/Isomerases; EC 5.3.-/Intramolecular Oxidoreductases; EC 5.3.99.4/prostacyclin synthetase; EC 5.3.99.5/Thromboxane-A Synthase

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