Biomaterial Database

Arachidonic acid metabolism modulates vasopressin-induced renal vasoconstriction. 1995

B Vazquez, and A Rios, and B Escalante

Department of Pharmacology ENEP Iztacala, UNAM, Mexico DF.

Previous studies have shown that cytochrome P450-Arachidonic Acid (P450-AA) metabolites modify the vascular tone of several vessels and that vasopressin (AVP) stimulates P450-AA metabolism. Thus, in the present study, we decided to investigate if the vasoconstrictor effect of AVP is related to activation of P450-AA metabolism. We used the isolated perfused kidney of a rat, to test this hypothesis. Bolus injection of AVP (5.5, 11, 22 and 45 ng) increased the perfusion pressure of the isolated kidney of a rat by 66 +/- 2, 87 +/- 4, 110 +/- 2 and 130 +/- 3 mmHg respectively. This AVP-induced vasoconstriction was significantly reduced by inhibition of AA metabolism with ETYA, or 7 ethoxyresorsorufin (7ER). Furthermore, in vivo induction of P450 system with dexamethasone, enhanced the AVP-induced vasoconstrictor effect. Conversely, depletion of P450 system with SnCl2 diminished the vasoconstrictor response to AVP. Measurement of P450-14cAA metabolites in the renal effluent, showed the presence of 3 radioactive peaks. The % of the recovered radioactivity was 0.12 +/- 0.05%, 0.11 +/- 0.03% and 1.13 +/- 0.5% and corresponded to Dihydroxyeicosatrienoic acids (DHTs), Hydroxyeicosatetraenoic acids (HETEs) and Epoxyeicosatrienoic acids (EETs) respectively, when kidneys were stimulated by AVP (300 ng) the % recovered were 0.34 +/- 0.01%, 0.38 +/- 0.01% and 3.11 +/- 0.7% for the DHTs, HETEs and EETs respectively. Treatment with dexamethasone or SnCl2 potentiated or inhibited the AVP-dependent release of the P450-AA metabolites. In conclusion, we suggest that AVP stimulates AA metabolism via P450 pathway in the kidney and that these AA metabolites participate in the vasoconstrictor effect of AVP in the renal circulation.

UI	MeSH Term	Description	Entries
D007668	Kidney	Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.	Kidneys
D008297	Male		Males
D010477	Perfusion	Treatment process involving the injection of fluid into an organ or tissue.	Perfusions
D011189	Potassium Chloride	A white crystal or crystalline powder used in BUFFERS; FERTILIZERS; and EXPLOSIVES. It can be used to replenish ELECTROLYTES and restore WATER-ELECTROLYTE BALANCE in treating HYPOKALEMIA.	Slow-K,Chloride, Potassium
D012079	Renal Circulation	The circulation of the BLOOD through the vessels of the KIDNEY.	Kidney Circulation,Renal Blood Flow,Circulation, Kidney,Circulation, Renal,Blood Flow, Renal,Flow, Renal Blood
D002250	Carbon Radioisotopes	Unstable isotopes of carbon that decay or disintegrate emitting radiation. C atoms with atomic weights 10, 11, and 14-16 are radioactive carbon isotopes.	Radioisotopes, Carbon
D003577	Cytochrome P-450 Enzyme System	A superfamily of hundreds of closely related HEMEPROTEINS found throughout the phylogenetic spectrum, from animals, plants, fungi, to bacteria. They include numerous complex monooxygenases (MIXED FUNCTION OXYGENASES). In animals, these P-450 enzymes serve two major functions: (1) biosynthesis of steroids, fatty acids, and bile acids; (2) metabolism of endogenous and a wide variety of exogenous substrates, such as toxins and drugs (BIOTRANSFORMATION). They are classified, according to their sequence similarities rather than functions, into CYP gene families (>40% homology) and subfamilies (>59% homology). For example, enzymes from the CYP1, CYP2, and CYP3 gene families are responsible for most drug metabolism.	Cytochrome P-450,Cytochrome P-450 Enzyme,Cytochrome P-450-Dependent Monooxygenase,P-450 Enzyme,P450 Enzyme,CYP450 Family,CYP450 Superfamily,Cytochrome P-450 Enzymes,Cytochrome P-450 Families,Cytochrome P-450 Monooxygenase,Cytochrome P-450 Oxygenase,Cytochrome P-450 Superfamily,Cytochrome P450,Cytochrome P450 Superfamily,Cytochrome p450 Families,P-450 Enzymes,P450 Enzymes,Cytochrome P 450,Cytochrome P 450 Dependent Monooxygenase,Cytochrome P 450 Enzyme,Cytochrome P 450 Enzyme System,Cytochrome P 450 Enzymes,Cytochrome P 450 Families,Cytochrome P 450 Monooxygenase,Cytochrome P 450 Oxygenase,Cytochrome P 450 Superfamily,Enzyme, Cytochrome P-450,Enzyme, P-450,Enzyme, P450,Enzymes, Cytochrome P-450,Enzymes, P-450,Enzymes, P450,Monooxygenase, Cytochrome P-450,Monooxygenase, Cytochrome P-450-Dependent,P 450 Enzyme,P 450 Enzymes,P-450 Enzyme, Cytochrome,P-450 Enzymes, Cytochrome,Superfamily, CYP450,Superfamily, Cytochrome P-450,Superfamily, Cytochrome P450
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D001127	Arginine Vasopressin	The predominant form of mammalian antidiuretic hormone. It is a nonapeptide containing an ARGININE at residue 8 and two disulfide-linked cysteines at residues of 1 and 6. Arg-vasopressin is used to treat DIABETES INSIPIDUS or to improve vasomotor tone and BLOOD PRESSURE.	Argipressin,Vasopressin, Arginine,Arg-Vasopressin,Argipressin Tannate,Arg Vasopressin
D014661	Vasoconstriction	The physiological narrowing of BLOOD VESSELS by contraction of the VASCULAR SMOOTH MUSCLE.	Vasoconstrictions