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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
1990-5-1
pubmed:abstractText
In the rat, intrarenal infusion of epidermal growth factor decreases renal blood flow and glomerular filtration rate, and epidermal growth factor (EGF) induces contraction of cultured rat mesangial cells. The present studies examined the role of arachidonic acid metabolites in this response. Intrarenal EGF infusion increased urinary iPGF2 alpha by 300%, and in isolated glomeruli EGF stimulated iPGF2 alpha by 38%, but did not affect thromboxane B2 production. Furthermore, the thromboxane A2 receptor antagonist, SQ29548, did not block EGF's vasoconstrictive effects. After selective cyclooxygenase inhibition with ibuprofen, intrarenal EGF infusion no longer produced local vasoconstriction but instead led to systemic vasodilation (SBP: 117 +/- 10 vs. 98 +/- 7; n = 5; P less than 0.05) that was accompanied by significant increases in RPF (3.8 +/- 0.4 vs. 5.6 +/- 0.2; P less than 0.01) and glomerular filtration rate (0.9 +/- 0.1 vs. 1.1 +/- 0.1; P less than 0.05). When total arachidonate metabolism was inhibited by the additional administration of 5,8,11,14-eicosatetraynoic acid, the EGF-induced vasodilation observed during cyclooxygenase inhibition alone was abolished, and vasoconstrictor responses to EGF were again noted. Similar effects were noted with concomitant administration of the c-P450 inhibitor ketoconazole. EGF's vasoconstrictive effects were unaltered by the simultaneous administration of the angiotensin II antagonist saralasin. Thus, the renal hemodynamic responses to EGF are mediated in part by arachidonic acid metabolites. Cyclooxygenase inhibition unmasks a potent renal and systemic vasodilator action of EGF owing to its stimulation of systemic release of noncyclooxygenase arachidonate metabolites.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0892-6638
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
4
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1654-60
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1990
pubmed:articleTitle
Mediation of renal vascular effects of epidermal growth factor by arachidonate metabolites.
pubmed:affiliation
Division of Nephrology, Vanderbilt University Medical Center, Nashville, Tennessee 37212.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S.