Modulation by 20-HETE of phenylephrine-induced mesenteric artery contraction in spontaneously hypertensive and Wistar-Kyoto rats

Fan Zhang, Mong Heng Wang, U. Murali Krishna, John R. Falck, Michal Laniado-Schwartzman, Alberto Nasjletti

Research output: Contribution to journalArticle

50 Scopus citations

Abstract

Small mesenteric arteries of spontaneously hypertensive (SHR) and Wistar-Kyoto rats (WKY) were compared for the production of 20-HETE and the effects of 20-HETE and N-methylsulfonyl-12,12-dibromododec-11-enamide (DDMS, 30 μmol/L), a 20-HETE synthesis inhibitor, on contractile responsiveness to phenylephrine (0.1 to 50.0 μmol/L). 20-HETE production was higher in vessels of SHR compared with WKY (1.34±0.16 versus 0.27±0.09 pmol/mg tissue, P<0.05). Phenylephrine elicited concentration-dependent vascular contraction; the Rmax was similar in vessels of SHR and WKY, but the former were more sensitive as denoted by the lower EC50 (1.10±0.14 versus 1.89±0.33 μmol/L, P<0.05). DDMS caused a rightward shift in the concentration-response curve to phenylephrine, increasing (P<0.05) the EC50 by 258% and 134% in vessels of SHR and WKY, respectively. In contrast, in DDMS-treated vessels, 20-HETE (0.01 to 10.0 μmol/L) caused a leftward shift in the phenylephrine concentration-response curve, decreasing (P<0.05) the EC50 without affecting the Rmax. Importantly, the minimal concentration of 20-HETE that decreased the EC50 of phenylephrine was much smaller in vessels of SHR that of WKY (0.01 versus 1.0 μmol/L). We conclude that 20-HETE increases the sensitivity of mesenteric arterial vessels to phenylephrine, vessels of SHR are more sensitive to this action of the eicosanoid than vessels of WKY, and vessels of SHR produce more 20-HETE than do vessels of WKY. Hence, 20-HETE of vascular origin may be a determinant of the increased reactivity to constrictor agonists in the vasculature of SHR.

Original languageEnglish (US)
Pages (from-to)1311-1315
Number of pages5
JournalHypertension
Volume38
Issue number6
DOIs
StatePublished - 2001

Keywords

  • 20-HETE
  • Eicosanoids
  • Vascular reactivity
  • Vasoconstriction

ASJC Scopus subject areas

  • Internal Medicine

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