Arachidonic acid metabolism modulates vasopressin-induced renal vasoconstriction.
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.
Vazquez
B
B
Department of Pharmacology ENEP Iztacala, UNAM, Mexico DF.
Rios
A
A
Escalante
B
B
D015117:5,8,11,14-Eicosatetraynoic Acid / Q000494:pharmacology; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D001127:Arginine Vasopressin / Q000494:pharmacology*; D002250:Carbon Radioisotopes; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D007668:Kidney / Q000098:blood supply* / Q000502:physiology; D008297:Male; D010477:Perfusion; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000187:drug effects / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology
D002250:Carbon Radioisotopes; D001127:Arginine Vasopressin; D015117:5,8,11,14-Eicosatetraynoic Acid; D016718:Arachidonic Acid; D011189:Potassium Chloride; D003577:Cytochrome P-450 Enzyme System