title: Enhanced endothelin receptor type B-mediated vasodilation and underlying [Ca²⁺]i in mesenteric microvessels of pregnant rats.
abstract: OBJECTIVE
  Normal pregnancy is associated with decreased vascular resistance and increased release of vasodilators. Endothelin-1 (ET-1) causes vasoconstriction via endothelin receptor type A (ET(A)R), but could activate ET(B)R in the endothelium and release vasodilator substances. However, the roles of ET(B)R in the regulation of vascular function during pregnancy and the vascular mediators involved are unclear.
  
  
  METHODS
  Pressurized mesenteric microvessels from pregnant and virgin Sprague-Dawley rats were loaded with fura-2/AM for simultaneous measurement of diameter and [Ca²⁺]i.
  
  
  RESULTS
  High KCl (51 mM) and phenylephrine (PHE) caused increases in vasoconstriction and [Ca²⁺]i that were similar in pregnant and virgin rats. ET-1 caused vasoconstriction that was less in pregnant than virgin rats, with small increases in [Ca²⁺]i. Pretreatment with the ET(B)R antagonist BQ-788 caused greater enhancement of ET-1-induced vasoconstriction in pregnant rats. ACh caused endothelium-dependent relaxation and decreased [Ca²⁺]i, and was more potent in pregnant than in virgin rats. ET-1 + ET(A)R antagonist BQ-123, and the ET(B)R agonists sarafotoxin 6c (S6c) and IRL-1620 caused greater vasodilation in pregnant than in virgin rats with no changes in [Ca²⁺]i, suggesting up-regulated ET(B)R-mediated relaxation pathways. ACh-, S6c- and IRL-1620-induced relaxation was reduced by the NO synthase inhibitor Nω-nitro-L-arginine methyl ester, and abolished by tetraethylammonium or endothelium removal. Western blots revealed greater amount of ET(B)R in intact microvessels of pregnant than virgin rats, but reduced levels in endothelium-denuded microvessels, supporting a role of endothelial ET(B)R.
  
  
  CONCLUSIONS
  The enhanced ET(B)R-mediated microvascular relaxation may contribute to the decreased vasoconstriction and vascular resistance during pregnancy.
authors: Vascular Surgery Research Laboratory, Division of Vascular and Endovascular Surgery, Harvard Medical School, Brigham and Women's Hospital, Boston, MA 02115, USA.
authors: Marc Q
authors: MQ
authors: Mazzuca
authors: Yiping
authors: Y
authors: Dang
authors: Raouf A
authors: RA
authors: Khalil
mesh_terms: D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D065130:Endothelin A Receptor Antagonists; D019332:Endothelin-1 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000201:enzymology / Q000502:physiology; D005260:Female; D066298:In Vitro Techniques; D008638:Mesenteric Arteries / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D008642:Mesenteric Veins / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D055806:Microvessels / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors / Q000378:metabolism; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D044022:Receptor, Endothelin A / Q000819:agonists / Q000378:metabolism; D044023:Receptor, Endothelin B / Q000737:chemistry / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D065130:Endothelin A Receptor Antagonists; D019332:Endothelin-1; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat
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