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

Autor: Fan Zhang, Mong Heng Wang, John R. Falck, U. Murali Krishna, Michal Laniado-Schwartzman, Alberto Nasjletti
Rok vydání: 2001
Předmět:
Zdroj: Hypertension (Dallas, Tex. : 1979). 38(6)
ISSN: 1524-4563
Popis: 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 max was similar in vessels of SHR and WKY, but the former were more sensitive as denoted by the lower EC 50 (1.10±0.14 versus 1.89±0.33 μmol/L, P P 50 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 50 without affecting the R max . Importantly, the minimal concentration of 20-HETE that decreased the EC 50 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.
Databáze: OpenAIRE