Contractility of placental vascular smooth muscle cells in response to stimuli produced by the placenta: roles of ACE vs. non-ACE and AT1 vs. AT2 in placental vessel cells.
Our previously published work has shown that non-ACE angiotensin II (Ang II) generating system is dominate in the placenta and may play a critical role in regulation of placental vascular contractile function. In the present study, using a collagen gel contraction assay we further studied contractility of placental vascular smooth muscle cells (VSMCs) in response to factors produced by preeclamptic (PE) placentas. Placental VSMCs/type-1 collagen gels were incubated with PE placental conditioned medium in the presence or absence of inhibitors or receptor blockers. Captopril (an ACE inhibitor), chymostatin (a non-ACE chymase inhibitor), losartan (an AT1 receptor blocker) and PD123,319 (an AT2 receptor blocker) were used to study the specific ACE vs. non-ACE and AT1 vs. AT2 effects on placental VSMC contractility, respectively. Our results showed that chymostatin, but not captopril, and PD123,319, but not losartan, significantly attenuated placental VSMC/collagen gel contraction, p<0.01, respectively. The inhibitory effects of chymostatin and PD123,319 were dose-dependent. Our results suggest that chymase, a non-ACE Ang II generating enzyme, may contribute significantly to Ang II generated in the placenta vascular tissue and that the AT2 receptor may play an important role in the regulation of Ang II induced contractility of placental VSMCs. These results provide new insights into Ang II generation and Ang II receptor regulation of vessel contractile function in the placental vasculature. These results also suggest the potential role of increased chymase activity and altered AT2 receptor function in placental related pregnancy disorders such as preeclampsia and IUGR.
Benoit
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C
Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, LA 71130, USA.
Gu
Y
Y
Zhang
Y
Y
Alexander
J S
JS
Wang
Y
Y
D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D057912:Angiotensin II Type 2 Receptor Blockers; D001808:Blood Vessels / Q000378:metabolism / Q000502:physiology*; D003094:Collagen / Q000494:pharmacology; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D009842:Oligopeptides / Q000494:pharmacology; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism / Q000502:physiology*; D010920:Placenta / Q000098:blood supply* / Q000378:metabolism / Q000502:physiology*; D011247:Pregnancy; D011725:Pyridines / Q000494:pharmacology; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism / Q000502:physiology*; D044139:Receptor, Angiotensin, Type 2 / Q000378:metabolism / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000378:metabolism / Q000494:pharmacology
D047228:Angiotensin II Type 1 Receptor Blockers; D057912:Angiotensin II Type 2 Receptor Blockers; D007093:Imidazoles; D009842:Oligopeptides; D011725:Pyridines; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D014662:Vasoconstrictor Agents; C073402:PD 123319; D003094:Collagen; C002101:chymostatin; D007703:Peptidyl-Dipeptidase A