LPA receptor-mediated thromboxane A release is responsible for lysophosphatidic acid-induced vascular smooth muscle contraction.

Lysophosphatidic acid (LPA) has been recognized recently as an endothelium-dependent vasodilator, but several lines of evidence indicate that it may also stimulate vascular smooth muscle cells (VSMCs), thereby contributing to vasoregulation and remodeling. In the present study, mRNA expression of all 6 LPA receptor genes was detected in murine aortic VSMCs, with the highest levels of LPA, LPA, LPA, and LPA In endothelium-denuded thoracic aorta (TA) and abdominal aorta (AA) segments, 1-oleoyl-LPA and the LPA agonist VPC31143 induced dose-dependent vasoconstriction. VPC31143-induced AA contraction was sensitive to pertussis toxin (PTX), the LPA antagonist Ki16425, and genetic deletion of LPA but not that of LPA or inhibition of LPA, by diacylglycerol pyrophosphate.