Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2 Pt 2
pubmed:dateCreated
1998-9-16
pubmed:abstractText
The mechanism-based cytochrome P-450 (CYP) inhibitor 1-aminobenzotriazole (ABT) was characterized as an inhibitor of renal arachidonic acid metabolism and administered to spontaneously hypertensive rats (SHRs) to determine the effect of reduced eicosanoid production on mean arterial pressure (MAP). A single intraperitoneal dose of ABT to Sprague-Dawley rats caused a dose-dependent loss of renal CYP content, arachidonic acid metabolism, and CYP4A protein. In the cortex and outer medulla, ABT showed a high degree of selectivity for the CYP4A enzymes, reflected by the potent inhibition of 19- and 20-hydroxyeicosatetraenoic acid (19- and 20-HETE) formation. A 50 mg/kg dose of ABT reduced cortical 20-HETE formation to 16.1 +/- 0.82% of control and outer medullary 20-HETE formation to 23.8 +/- 0.45% of control. In contrast, there was no inhibition of renal epoxygenase activity at this dose. Renal CYP content, arachidonic acid omega- and (omega-1)-hydroxylase activity, and CYP4A protein levels gradually return to control levels by 72 h after a single dose of ABT. Cortical 20-HETE formation recovered from 17.9 +/- 3.15% of control at 6 h to 84.8 +/- 4.67% of control at 72 h after ABT administration. A single injection of ABT to 7-wk-old SHRs caused an acute reduction in MAP, which remained suppressed for at least 12 h. The effect was maximal within 4 h and averaged 17-23 mmHg during the 4- to 12-h period after administration. 20-HETE formation was inhibited 85% in the cortex and 70-80% in the outer medulla during the period when MAP was reduced. A structurally related ABT analog 1-hydroxybenzotriazole had no effect on blood pressure or renal arachidonic acid metabolism. These results identify ABT as a selective inhibitor of renal CYP4A activity and provide further support for a role for 20-HETE in the regulation of blood pressure.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0002-9513
pubmed:author
pubmed:issnType
Print
pubmed:volume
275
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
R426-38
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:9688677-Alkane 1-Monooxygenase, pubmed-meshheading:9688677-Animals, pubmed-meshheading:9688677-Blood Pressure, pubmed-meshheading:9688677-Cytochrome P-450 Enzyme System, pubmed-meshheading:9688677-Hydroxyeicosatetraenoic Acids, pubmed-meshheading:9688677-Hypertension, pubmed-meshheading:9688677-Kidney, pubmed-meshheading:9688677-Kidney Cortex, pubmed-meshheading:9688677-Kidney Medulla, pubmed-meshheading:9688677-Kinetics, pubmed-meshheading:9688677-Male, pubmed-meshheading:9688677-Microsomes, pubmed-meshheading:9688677-Microsomes, Liver, pubmed-meshheading:9688677-Mixed Function Oxygenases, pubmed-meshheading:9688677-Rats, pubmed-meshheading:9688677-Rats, Inbred SHR, pubmed-meshheading:9688677-Rats, Sprague-Dawley, pubmed-meshheading:9688677-Reference Values, pubmed-meshheading:9688677-Triazoles
pubmed:year
1998
pubmed:articleTitle
Inhibition of renal arachidonic acid omega-hydroxylase activity with ABT reduces blood pressure in the SHR.
pubmed:affiliation
Department of Biopharmaceutical Sciences, School of Pharmacy, University of California San Francisco, San Francisco, California 94143, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't