Lipoxygenase-dependent mechanisms in hypertension.
This study was designed to examine the contribution of lipoxygenase products to mechanisms of vascular contraction and elevated blood pressure in rats with aortic coarctation-induced hypertension. In cytosolic fractions of aortae taken from hypertensive rats, 12-lipoxygenase protein was increased as compared to normotensive controls. Aortic rings from hypertensive, but not from normotensive rats, exhibited a basal tone which was reduced 74+/-12 and 71+/-22%, respectively, by the lipoxygenase inhibitors cinnamyl-3,4-dihydroxy-alpha-cyanocinnamate (CDC, 10(-5) mol/L) and 5,8,11-eicosatriynoic acid (ETI, 10(-5) mol/L). CDC (8 mg/kg s.c.) did not affect the blood pressure of normotensive rats but decreased that of hypertensive rats from 182+/-6 to 151+/-10 mm Hg. The blood pressure lowering effect of CDC was blunted in hypertensive rats pretreated with indomethacin or antibodies against 5,6-dihydro-prostaglandin I2. These data suggest contribution of lipoxygenase-derived products to mechanisms underlying aortic smooth muscle basal tone and elevated blood pressure in rats with aortic coarctation-induced hypertension. The vasodepressor effect of CDC depends on a mechanism involving vasodilatory prostaglandins.
DelliPizzi
A
A
Department of Pharmacology, New York Medical College, Valhalla 10595, USA.
Guan
H
H
Tong
X
X
Takizawa
H
H
Nasjletti
A
A
D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid / Q000494:pharmacology; D015126:8,11,14-Eicosatrienoic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000201:enzymology / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002109:Caffeic Acids / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004195:Disease Models, Animal; D011464:Epoprostenol / Q000031:analogs & derivatives / Q000276:immunology / Q000494:pharmacology; D006973:Hypertension / Q000201:enzymology* / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control; D007213:Indomethacin / Q000494:pharmacology; D015289:Leukotrienes / Q000494:pharmacology; D008084:Lipoxygenase / Q000187:drug effects / Q000378:metabolism*; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000201:enzymology / Q000503:physiopathology; D011465:Prostaglandins, Synthetic / Q000276:immunology / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D002109:Caffeic Acids; D016861:Cyclooxygenase Inhibitors; D015289:Leukotrienes; D016859:Lipoxygenase Inhibitors; D011465:Prostaglandins, Synthetic; D014662:Vasoconstrictor Agents; C099255:cinnamyl-3,4-dihydroxycyanocinnamate; C061163:11-glutathionylhepoxilin A3; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; C022228:5,6-dihydroprostacyclin; C021201:12-HPETE; D011464:Epoprostenol; D008084:Lipoxygenase; D015126:8,11,14-Eicosatrienoic Acid; D007213:Indomethacin