Cytochrome P450 metabolites of arachidonic acid may be important mediators in angiotensin II-induced vasoconstriction in the rat mesentery in vivo

Z. M. Chu, K. D. Croft, D. A. Kingsbury, J. R. Falck, K. M. Reddy, L. J. Beilin

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

We have investigated the role of cytochrome P450 (CYP-450) metabolites of arachidonic acid in the modulation of vascular reactivity to angiotensin II in vivo using an in situ blood-perfused mesenteric preparation in anaesthetized spontaneously hypertensive rats (SHR). Miconazole, a non-selective inhibitor of CYP-450 that inhibits both hydroxylation and epoxidation, substantially suppressed mesenteric vasoconstrictor responses to angiotensin II in SHR, but had no effect on responses to noradrenaline or sympathetic nerve stimulation. In normotensive Wistar-Kyoto (WKY) rats, miconazole caused only a modest suppression of vasoconstrictor responses to angiotensin II. N-Methylsulphonyl-12, 12-dibromododec-I I-enamide (DDMS), a new selective inhibitor of CYP-450 ω-hydroxylase activity, decreased mean intra-arterial blood pressure and significantly attenuated mesenteric angiotensin II-induced vasoconstrictor responses in SHR. Isolated mesenteric vessels were able to metabolize 14C-labelled arachidonic acid to hydroxyeicosatetraenoic acids (HETEs) in vitro, and this was substantially inhibited by DDMS. The results from the present studies combined with the existing evidence that angiotensin II stimulates the release of 20-HETE, a CYP-450 metabolite of arachidonic acid, suggest that CYP-450-derived HETEs may be important mediators in angiotensin II-induced asoconstriction. However, the development of more sensitive assays for the detection in vivo of 20-HETE in mesenteric vessels would be required to confirm these findings.

Original languageEnglish (US)
Pages (from-to)277-282
Number of pages6
JournalClinical Science
Volume98
Issue number3
StatePublished - 2000

Fingerprint

Mesentery
Vasoconstriction
Arachidonic Acid
Angiotensin II
Cytochrome P-450 Enzyme System
Hydroxyeicosatetraenoic Acids
Vasoconstrictor Agents
Inbred SHR Rats
Miconazole
Inbred WKY Rats
Hydroxylation
Mixed Function Oxygenases
Blood Vessels
Norepinephrine
Arterial Pressure

Keywords

  • Cytochrome P450
  • Spontaneously hypertensive rat
  • Vasoconstriction

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Cytochrome P450 metabolites of arachidonic acid may be important mediators in angiotensin II-induced vasoconstriction in the rat mesentery in vivo. / Chu, Z. M.; Croft, K. D.; Kingsbury, D. A.; Falck, J. R.; Reddy, K. M.; Beilin, L. J.

In: Clinical Science, Vol. 98, No. 3, 2000, p. 277-282.

Research output: Contribution to journalArticle

Chu, Z. M. ; Croft, K. D. ; Kingsbury, D. A. ; Falck, J. R. ; Reddy, K. M. ; Beilin, L. J. / Cytochrome P450 metabolites of arachidonic acid may be important mediators in angiotensin II-induced vasoconstriction in the rat mesentery in vivo. In: Clinical Science. 2000 ; Vol. 98, No. 3. pp. 277-282.
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