CYP4A1 antisense oligonucleotide reduces mesenteric vascular reactivity and blood pressure in SHR

Mong-Heng Wang, Fan Zhang, Jackleen Marji, Barbara A. Zand, Alberto Nasjletti, Michal Laniado-Schwartzman

Research output: Contribution to journalArticle

104 Scopus citations

Abstract

The cytochrome P-450 4A (CYP4A)-derived arachidonic acid metabolite 20-hydroxyeicosatetraenoic acid (20-HETE) affects renal tubular and vascular functions and has been implicated in the control of arterial pressure. We examined the effect of antisense oligonucleotide (ODN) to CYP4A1, the low Km arachidonic acid ω-hydroxylating isoform, on vascular 20-HETE synthesis, vascular reactivity, and blood pressure in the spontaneously hypertensive rat (SHR). Administration of CYP4A1 antisense ODN decreased mean arterial blood pressure from 137 ± 3 to 121 ± 4 mmHg (P < 0.05) after 5 days of treatment, whereas treatment with scrambled antisense ODN had no effect. Treatment with CYP4A1 antisense ODN reduced the level of CYP4A-immunoreactive proteins along with 20-HETE synthesis in mesenteric arterial vessels. Mesenteric arteries from rats treated with antisense ODN exhibited decreased sensitivity to the constrictor action of phenylephrine (EC50 0.69 ± 0.17 vs. 1.77 ± 0.40 μM). Likewise, mesenteric arterioles from antisense ODN-treated rats revealed attenuation of myogenic constrictor responses to increases of transmural pressure. The decreased vascular reactivity and myogenic responses were reversible with the addition of 20-HETE. These data suggest that CYP4A1-derived 20-HETE facilitates myogenic constrictor responses in the mesenteric microcirculation and contributes to pressor mechanisms in SHR.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume280
Issue number1 49-1
StatePublished - Jan 1 2001
Externally publishedYes

    Fingerprint

Keywords

  • 20-hydroxyeicosatetraenoic acid
  • Blood pressure
  • Kidney
  • Myogenic response
  • Phenylephrine

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this