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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4 Pt 1
pubmed:dateCreated
1997-7-1
pubmed:abstractText
We have previously demonstrated that administration of inhibitors of the lipoxygenase (LO) pathway of arachidonic acid metabolism lowers blood pressure in hypertensive rats. In addition, we have shown that LO inhibition attenuates pressor agonist-induced vascular reactivity in vitro and calcium mobilization in cultured vascular smooth muscle cells (VSMC). To further elucidate the relationship between elevated LO activity and hypertension, 4, 8, and 12 week old hypertensive SHR were compared with age-matched Wistar-Kyoto (WKY) rats for plasma 12(S)-hydroxyeicosatetraenoic acid (12-HETE) concentration. 12-HETE levels were significantly elevated in the SHR compared to the WKY (SHR elevated by 154%, 159%, and 272% compared to WKY at 4, 8, and 12 weeks, respectively, P < .01 for all ages). There were no differences in plasma potassium levels between SHR and WKY at any of the ages tested. Plasma aldosterone levels and plasma renin activity were in the normal range at the three ages. At 12 weeks of age, both serum (4.72 +/- 0.23 v 2.18 +/- 0.33 microg/mL, P < .01), and aortic smooth muscle 12-HETE levels (0.94 +/- 0.09 v 0.66 +/- 0.08 microg/mg protein, P < .05) were elevated in SHR compared with WKY. The 12 week old SHR were given a bolus of the LO inhibitor 5,8,11-eicosatriynoic acid (ETI, 7 mg/kg, intravenously) and blood pressure measured after 20 min. ETI reduced mean systolic blood pressure from 175.8 +/- 4.2 to 141.6 +/- 5.9 mm Hg (P < .05). To investigate these effects of HETEs, cultured vascular smooth muscle cells were pretreated for 1 min with 12(S)HETE and then challenged with angiotensin II (AngII). The addition of 12(S)HETE increased AngII-induced intracellular calcium levels in normal cultured rat vascular smooth muscle cells by 78% compared to vehicle (P < .05). Thus, LO products, which are high in SHR, may contribute to vascular tone through alterations in the intracellular calcium signal by potentiating calcium responses to pressors such as Ang II.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0895-7061
pubmed:author
pubmed:issnType
Print
pubmed:volume
10
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
371-8
pubmed:dateRevised
2009-2-24
pubmed:meshHeading
pubmed:year
1997
pubmed:articleTitle
Elevated 12-lipoxygenase activity in the spontaneously hypertensive rat.
pubmed:affiliation
Division of Endocrinology, Department of Veteran's Affairs Medical Center, Sepulveda, California 91343, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.