title: Shear stress-dependent effects of lysophosphatidic acid on agonist-induced vasomotor responses in rat mesenteric artery.
abstract: We have previously shown that lysophosphatidic acid (LPA), a bioactive plasma lysophospholipid, markedly accelerates shear stress-induced Ca2+ responses in cultured vascular endothelial cells (ECs). This study aimed to demonstrate the impact of LPA and luminal shear stress on vasomotor regulation in the isolated rat mesenteric artery (MA) using a videomicroscopic technique. Although the addition of LPA to the perfusate in a concentration range of 0.03-0.3 μM had no significant effect on the basal MA tone, LPA in a similar concentration range led to increased phenylephrine-induced MA contraction and reduced acetylcholine-induced MA relaxation under physiological shear conditions. These vasomodulatory actions of LPA, which vanished upon removal of ECs, were positively dependent on luminal shear stress levels and were markedly inhibited by the LPA receptor antagonist Ki16425, the cyclooxygenase inhibitor indomethacin, and the thromboxane A2 receptor antagonist SQ29548. These data thus suggest that LPA can modify the agonist-induced vasomotor responses in MAs in a shear stress-dependent manner. This effect of LPA was mediated through ECs, the LPA receptor, and cyclooxygenase/thromboxane A2 signaling.
authors.affiliation: Department of Pharmacology, School of Pharmacy, Showa University, Tokyo, Japan. kshibata@pharm.showa-u.ac.jp
authors.forename: Keita
authors.initials: K
authors.lastname: Shibata
authors.forename: Takuro
authors.initials: T
authors.lastname: Miyazaki
authors.forename: Hisayuki
authors.initials: H
authors.lastname: Ohata
authors.forename: Kazuo
authors.initials: K
authors.lastname: Honda
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D002118:Calcium / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D066298:In Vitro Techniques; D008246:Lysophospholipids / Q000494:pharmacology*; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D018715:Microscopy, Video; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D049368:Receptors, Lysophosphatidic Acid / Q000819:agonists* / Q000037:antagonists & inhibitors; D013314:Stress, Mechanical; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology
chemical_list: D008246:Lysophospholipids; D049368:Receptors, Lysophosphatidic Acid; C032881:lysophosphatidic acid; D002118:Calcium