Role of hyaluronic acid glycosaminoglycans in shear-induced endothelium-derived nitric oxide release.
Endothelium-derived nitric oxide (NO) is synthesized in response to chemical and physical stimuli. Here, we investigated a possible role of the endothelial cell glycocalyx as a biomechanical sensor that triggers endothelial NO production by transmitting flow-related shear forces to the endothelial membrane. Isolated canine femoral arteries were perfused with a Krebs-Henseleit solution at a wide range of perfusion rates with and without pretreatment with hyaluronidase to degrade hyaluronic acid glycosaminoglycans within the glycocalyx layer. NO production rate was evaluated as the product of nitrite concentration in the perfusate and steady-state perfusion rate. The slope that correlates the linear relation between perfusion rate and NO production rate was taken as a measure for flow-induced NO production. Hyaluronidase treatment significantly decreased flow-induced NO production to 19 +/- 9% of control (mean +/- SD; P < 0.0001 vs. control; n = 11), whereas it did not affect acetylcholine-induced NO production (88 +/- 17% of pretreatment level, P = not significant; n = 10). We conclude that hyaluronic acid glycosaminoglycans within the glycocalyx play a pivotal role in detecting and amplifying the shear force of flowing blood that triggers endothelium-derived NO production in isolated canine femoral arteries.
Department of Medical Engineering, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama 701-0192, Japan. mochi@me.kawasaki-m.ac.jp
Seiichi
S
Mochizuki
Hans
H
Vink
Osamu
O
Hiramatsu
Tatsuya
T
Kajita
Fumiyuki
F
Shigeto
Jos A E
JA
Spaan
Fumihiko
F
Kajiya
D000818:Animals; D004285:Dogs; D004730:Endothelium, Vascular / Q000378:metabolism*; D005260:Female; D005263:Femoral Artery / Q000378:metabolism; D019276:Glycocalyx / Q000378:metabolism; D006025:Glycosaminoglycans / Q000378:metabolism*; D006820:Hyaluronic Acid / Q000378:metabolism*; D006821:Hyaluronoglucosaminidase / Q000378:metabolism; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D009573:Nitrites / Q000378:metabolism; D011673:Pulsatile Flow / Q000502:physiology; D013314:Stress, Mechanical
D006025:Glycosaminoglycans; D009573:Nitrites; D009569:Nitric Oxide; D006820:Hyaluronic Acid; D006821:Hyaluronoglucosaminidase