Nanoparticle inhalation impairs endothelium-dependent vasodilation in subepicardial arterioles.
Exposure to fine particulate matter (PM, mean aerodynamic diameter <or=2.5 microm) has been shown to be a risk factor for cardiovascular disease mortality and may contribute to acute coronary events such as myocardial infarction (MI). There is sufficient reason to believe that smaller particles, such as nanoparticles, might be even more detrimental than larger sized particles due to their increased surface area and higher pulmonary deposition. Our laboratory showed that nanoparticle inhalation impairs endothelium-dependent arteriolar vasodilation in skeletal muscle. However, it is not known whether coronary microvascular endothelial function is affected in a similar manner. Rats were exposed to filtered air (control) or TiO(2) nanoparticles (primary particle diameter, approximately 21 nm) via inhalation at concentrations that produced measured depositions (10 microg) relevant to ambient air pollution. Subepicardial arterioles ( approximately 150 mum in diameter) were isolated and responses to transmural pressure, flow-induced dilation (FID), acetylcholine (ACh), the Ca(2+) ionophore A23187, and sodium nitroprusside (SNP) were assessed. Myogenic responsiveness was preserved between groups. In addition, there was no difference in the vasodilation to SNP, signifying that smooth muscle sensitivity to nitric oxide (NO) is unaffected by nano-TiO(2) exposure. However, inhalation of nano-TiO(2) produced an increase in spontaneous tone in coronary arterioles and also impaired endothelium-dependent FID. In addition, ACh-induced and A23187-induced vasodilation was also blunted in arterioles after inhalation of nano-TiO(2). Data showed that nanoparticle exposure significantly impairs endothelium-dependent vasodilation in subepicardial arterioles. Such disturbances in coronary microvascular function are consistent with the cardiac events associated with particle pollution exposure.
LeBlanc
A J
AJ
Center for Cardiovascular and Respiratory Sciences, West Virginia University School of Medicine, Morgantown 26506-9105, West Virginia, USA.
Cumpston
J L
JL
Chen
B T
BT
Frazer
D
D
Castranova
V
V
Nurkiewicz
T R
TR
D000818:Animals; D001160:Arterioles / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D019570:Inhalation Exposure / Q000009:adverse effects*; D008297:Male; D053758:Nanoparticles / Q000737:chemistry / Q000633:toxicity*; D010316:Particle Size; D052638:Particulate Matter / Q000737:chemistry / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014025:Titanium / Q000633:toxicity*; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology
D052638:Particulate Matter; C009495:titanium dioxide; D014025:Titanium