OR-56: Cytochrome P450 products of arachidonate contribute to the differential control of renal cortical and medullary perfusion

• Published in: American journal of hypertension Vol. 16; no. S1; p. 26A
• Main Authors: Rajapakse, Niwanthi W., Falck, John R., Oliver, Jeremy J., Evans, Roger G.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.05.2003
• Subjects: Cytochrome P450; Renal cortical blood flow; Renal medullary blood flow
• ISSN: 0895-7061; 1941-7225; 1879-1905
• DOI: 10.1016/S0895-7061(03)00118-3

Cytochrome P450 (CYP450) metabolises arachidonate to 19- and 20-hydroxyeicosatetraenoic acid (19/20-HETE) and epoxyeicosatrienoic acids (EETs) via the ω-hydroxylase and epoxygenase pathways, respectively. We hypothesised that regionally-selective release of these metabolites contributes to the hormonal control of regional kidney perfusion. Our aim was to investigate the role of CYP450 arachidonate metabolites in responses of regional kidney perfusion to the V1- agonist [Phe2,Ile3,Orn8]-vasopressin and angiotensin II. A catheter was placed in a renal artery side branch of pentobarbitone anaesthetized rabbits. A transonic flow probe measured renal blood flow (RBF) and laser Doppler flow probes measured cortical and medullary perfusion (CBF and MBF). After equilibration, rabbits received renal arterial infusions of the CYP450 epoxygenase inhibitor N-methylsulfonyl-6-(2-propargyloxyphenyl) hexanoic acid (MS-PPOH; 2mg/kg + 1.5mg/kg/h; n=6), the ω-hydroxylase inhibitor N-methylsulfonyl-12-12,dibromododec-11-enamide (DDMS; 2mg/kg + 1.5mg/kg/h; n=6) or vehicle (45% hydroxypropyl-β-cyclodextran; n=6). Ascending doses of angiotensin II (2, 6 & 20ng/kg/min) and [Phe2,Ile3,Orn8]-vasopressin (3, 10 & 30ng/kg/min) were then administered into the renal artery. Compared with vehicle, neither MS-PPOH nor DDMS affected baseline mean arterial pressure, RBF, CBF or MBF. After vehicle, [Phe2,Ile3,Orn8]-vasopressin reduced MBF (up to 62±7%) but not CBF or RBF. MS-PPOH did not affect responses of MBF to [Phe2,Ile3,Orn8]-vasopressin, but revealed reductions in RBF (up to 51±8%) and CBF (up to 59±13%). DDMS did not significantly affect responses to [Phe2,Ile3,Orn8]-vasopressin. After vehicle, angiotensin II reduced RBF (up to 45±10%) and CBF (up to 41±14%) but not MBF. DDMS did not affect responses of RBF and CBF to angiotensin II, but revealed dose-dependent reductions in MBF (up to 24±14%). MS-PPOH did not significantly affect responses to angiotensin II. EETs may blunt V1-receptor mediated cortical vasoconstriction. 19/20-HETE or their metabolites may blunt angiotensin II mediated vasoconstriction in vascular elements controlling MBF.