An Endothelium-Derived Hyperpolarizing Factor–Like Factor Moderates Myogenic Constriction of Mesenteric Resistance Arteries in the Absence of Endothelial Nitric Oxide Synthase–Derived Nitric Oxide

• Ramona S. Scotland

  From the Centre for Clinical Pharmacology, University College London, The Rayne Institute, London, United Kingdom.

• Sharmila Chauhan

  From the Centre for Clinical Pharmacology, University College London, The Rayne Institute, London, United Kingdom.

• Patrick J.T. Vallance

  From the Centre for Clinical Pharmacology, University College London, The Rayne Institute, London, United Kingdom.

• Amrita Ahluwalia

  From the Centre for Clinical Pharmacology, University College London, The Rayne Institute, London, United Kingdom.

抄録

Myogenic tone is an important determinant of vascular tone and blood flow in small resistance arteries of certain vascular beds. The role of the endothelium in myogenic responses is unclear. We hypothesized that endothelium-derived NO release modulates myogenic constriction in small resistance arteries and that mesenteric small arteries from mice with targeted disruption of the gene for endothelial NO synthase (eNOS) (knockout mice) demonstrate greater myogenic tone than do wild-type mice. Third-order mesenteric arteries (≈200 μm) were isolated and mounted in a pressure myograph. Internal diameter was recorded over a pressure range of 10 to 80 mm Hg. Removal of the endothelium significantly ( P <0.05) enhanced the magnitude of myogenic constriction in wild-type mice. Similarly, pretreatment of arteries with N G -nitro- l -arginine methyl ester (L-NAME; 300 μmol/L) produced a comparable significant ( P <0.05) increase in myogenic tone, whereas indomethacin (5 μmol/L) had no effect. eNOS knockout arteries also exhibited myogenic constriction. Neither L-NAME nor indomethacin had any effect on myogenic tone in the arteries of eNOS knockout mice. However, blockade of potential endothelium-derived hyperpolarizing factor–like mechanisms via inhibition of K + flux using either apamin (100 nmol/L) with charybdotoxin (100 nmol/L), Ba 2+ (30 μmol/L) with ouabain (1 mmol/L), or 18α-glycyrrhetinic acid (100 μmol/L) significantly ( P <0.01) enhanced myogenic constriction. This study demonstrates that basal endothelium-derived NO modulates myogenic tone in mesenteric small arteries of wild-type mice. However, eNOS knockout arteries display normal myogenic responsiveness despite the absence of basal NO activity. The data suggest that this compensatory effect is due to the activity of an endothelium-derived hyperpolarizing factor to normalize vascular tone.

収録刊行物

• Hypertension

  Hypertension 38 (4), 833-839, 2001-10

  Ovid Technologies (Wolters Kluwer Health)

キーワード

• Internal Medicine

詳細情報

• CRID: 1362262944206480640
• NII論文ID: 30029739217
• DOI: 10.1161/hy1001.092651
• ISSN: 15244563
• ISSN: 0194911X
• Web Site: https://www.ahajournals.org/doi/full/10.1161/hy1001.092651
• データソース種別:
  • Crossref
  • CiNii Articles