Low-intensity ultrasound increases endothelial cell nitric oxide synthase activity and nitric oxide synthesis.
Low-intensity ultrasound (US) increases tissue perfusion in ischemic muscle through a nitric oxide (NO)-dependent mechanism. We have developed a model to expose endothelial cells to well-characterized acoustic fields in vitro and investigate the physical and biological mechanisms involved. Human umbilical vein endothelial cells (HUVEC) or bovine aortic endothelial cells (BAEC) were grown in tissue culture plates suspended in a temperature-controlled water bath and exposed to US. Exposure to 27 kHz continuous wave US at 0.25 W cm(-2) for 10 min increased HUVEC media NO by 102 +/- 19% (P < 0.05) and BAEC by 117 +/- 23% (P < 0.01). Endothelial cell NO synthase activity increased by 27 +/- 24% in HUVEC and by 32 +/- 16% in BAEC (P < 0.05 for each). The cell response was rapid with a significant increase in NO synthesis by 10 s and a maximum increase after exposure for 1 min. By 30 min post-exposure NO synthesis declined to baseline, indicating that the response was transient. Unexpectedly, pulsing at a 10% duty cycle resulted in a 46% increase in NO synthesis over the response seen with continuous wave US, resulting in an increase of 147 +/- 18%. Cells responded to very low intensity US, with a significant increase at 0.075 W cm(-2) (P < 0.01) and a maximum response at 0.125 W cm(-2). US caused minor reversible changes in cell morphology but did not alter proliferative capacity, indicating absence of injury. We conclude that exposure of endothelial cells to low-intensity, low-frequency US increases NO synthase activity and NO production, which could be used to induce vasodilatation experimentally or therapeutically.
Altland
O D
OD
Hematology/Oncology Unit, Department of Medicine, University of Rochester School of Medicine & Dentistry, Rochester, NY, USA.
Dalecki
D
D
Suchkova
V N
VN
Francis
C W
CW
D000818:Animals; D001011:Aorta; D002417:Cattle; D002455:Cell Division; D048429:Cell Size; D002478:Cells, Cultured; D004307:Dose-Response Relationship, Radiation; D042783:Endothelial Cells / Q000201:enzymology / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology; D006801:Humans; D009569:Nitric Oxide / Q000032:analysis / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000378:metabolism / Q000528:radiation effects*; D014465:Ultrasonics; D014471:Umbilical Veins
D009569:Nitric Oxide; D019001:Nitric Oxide Synthase