Role of the lipoxygenase pathway in angiotensin II-induced vasoconstriction in the human placenta.
We have previously shown that the vasopressor effect of angiotensin II (Ang II) is inhibited by lipoxygenase (LO) blockers. To elucidate the specific mechanism involved, we studied the relationship between the contractile effect of Ang II and LO products in a human placental preparation. In perfused placental cotyledons, Ang II (boluses of 1 to 10 microg) increased perfusion pressure and 12-hydroxyeicosatetraenoic acid (12-HETE) release. The LO blockers phenidone and n-propyl gallate reduced the maximal Ang II-induced increment in pressure from 26+/-3 to 16+/-3 and 18+/-4 mm Hg, respectively (P<.05 for both). Ang II alone (10 microg) increased 12-HETE release from 8.9+/-3.6 to 37.6+/-0.4 ng/min, and this rise was entirely blocked by both phenidone and n-propyl gallate. Pressure increase generated by an increase in flow rate had no effect on 12-HETE formation. In deendothelialized umbilical artery segments, Ang II (10(-7) mol/L) increased 12-HETE formation by 47+/-5% (n=20). In cultured umbilical artery smooth muscle cells, Ang II increased 12-HETE formation from 48.1+/-7.2 to 75.1+/-15.3 ng/mg protein, and this effect was also blocked by the specific LO inhibitor baicalein (10(-6) mol/L). These results provide evidence that the vasopressor effect of Ang II is functionally coupled to 12-LO activation, which apparently takes place in arterial smooth muscle cells.
Kisch
E S
ES
Institute of Endocrinology, Elias-Sourasky-Tel-Aviv Medical Center and Sackler Faculty of Medicine, Tel-Aviv University, Israel.
Jaffe
A
A
Knoll
E
E
Stern
N
N
D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid / Q000378:metabolism; D000804:Angiotensin II / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006801:Humans; D008084:Lipoxygenase / Q000378:metabolism*; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism*; D010920:Placenta / Q000098:blood supply / Q000187:drug effects*; D014469:Umbilical Arteries / Q000187:drug effects / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D016859:Lipoxygenase Inhibitors; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D008084:Lipoxygenase