Modulation by 20-HETE of phenylephrine-induced mesenteric artery contraction in spontaneously hypertensive and Wistar-Kyoto rats.
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 micromol/L), a 20-HETE synthesis inhibitor, on contractile responsiveness to phenylephrine (0.1 to 50.0 micromol/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 R(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 micromol/L, P<0.05). DDMS caused a rightward shift in the concentration-response curve to phenylephrine, increasing (P<0.05) the EC(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 micromol/L) caused a leftward shift in the phenylephrine concentration-response curve, decreasing (P<0.05) the EC(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 micromol/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.
Zhang
F
F
Department of Pharmacology, New York Medical College, Valhalla 10595, USA. fan_zhang@nymc.edu
Wang
M H
MH
Krishna
U M
UM
Falck
J R
JR
Laniado-Schwartzman
M
M
Nasjletti
A
A
D000577:Amides / Q000494:pharmacology; D000818:Animals; D019483:Disintegrins; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism*; D006973:Hypertension / Q000503:physiopathology*; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects; D008638:Mesenteric Arteries / Q000187:drug effects / Q000503:physiopathology; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013045:Species Specificity; D013450:Sulfones / Q000494:pharmacology; D014667:Vasopressins / Q000494:pharmacology; D014757:Viper Venoms
D000577:Amides; D019483:Disintegrins; C415464:EC6 protein, Echis carinatus sochureki; D004791:Enzyme Inhibitors; D006893:Hydroxyeicosatetraenoic Acids; D013450:Sulfones; D014757:Viper Venoms; D014667:Vasopressins; D010656:Phenylephrine; C055987:20-hydroxy-5,8,11,14-eicosatetraenoic acid; C117975:DDMS