Vascular CO counterbalances the sensitizing influence of 20-HETE on agonist-induced vasoconstriction

Jun Ichi Kaide, Fan Zhang, Yuan Wei, WenHui Wang, Venkat Raj Gopal, J R Falck, Michal Laniado-Schwartzman, Alberto Nasjletti

Research output: Contribution to journalArticlepeer-review

35 Scopus citations


We examined the influence of interactions between CO and 20-hydroxyeicosatetraenoic acid (20-HETE) on vascular reactivity to phenylephrine and vasopressin. Renal interlobar arteries incubated in Krebs buffer released CO at a rate that is decreased (from 125.0±15.2 to 46.3±8.8 μmol/mg protein per hour, P<0.05) by the heme oxygenase inhibitor chromium mesoporphyrin (CrMP; 30 μmol/L). The level of 20-HETE in vessels was not affected by CrMP (74.3±6.1 versus 72.5±16.2 μmol/mg protein), but was decreased (P<0.05) by CO (1 μmol/L; 33.2±7.9 μmol/mg protein) or the cytochrome P450-4A inhibitor N-methylsulfonyl-12,12-dibromododec-11-enamide (DDMS; 30 μmol/L; 11.4±3.3 μmol/mg protein). Phenylephrine elicited development of isometric tension in vascular rings mounted on a wire-myograph (EC50, 0.29±0.02 μmol/L; Rmax, 3.78±0.19 mN/mm). The sensitivity to phenylephrine was decreased (P<0.05) by CO (1 μmol/L; EC50, 0.60±0.04 μmol/L) or DDMS (EC50, 0.71±0.12 μmol/L) and increased (P<0.05) by 20-HETE (10 μmol/L; EC50, 0.08 ±0.02 μmol/L) or CrMP (EC50, 0.11±0.02 μmol/L). Notably, neither CO nor CrMP changed the sensitivity to phenylephrine in vessels treated with DDMS. Refractoriness to CO and CrMP in such a setting was eliminated by inclusion of 20-HETE (1 μmol/L) in the bathing buffer. The aforementioned interventions affected the vascular reactivity to vasopressin in a similar manner. These data indicate that the reactivity of renal arteries to phenylephrine and vasopressin is reciprocally influenced by CO and 20-HETE of vascular origin and that CO desensitizes the vascular smooth muscle to constrictor agonists by interfering with the sensitizing influence of 20-HETE.

Original languageEnglish (US)
Pages (from-to)210-216
Number of pages7
Issue number2
StatePublished - Aug 2004


  • Adrenergic receptor agonists
  • Potassium channels
  • Renal circulation
  • Vasopressins

ASJC Scopus subject areas

  • Internal Medicine


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