Nanoparticle inhalation impairs endothelium-dependent vasodilation in subepicardial arterioles

Abstract

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.

Figure 1

Active pressure responses of coronary arterioles of sham-control rats (n = 10) and nano-TiO₂ exposed rats (n = 11). Values are means ± S.E.

Figure 2

A) Vasodilatory responses to increases in intraluminal flow in sham-control rats (n = 10) and rats exposed to nano-TiO₂ (n = 10). Values are means ± S.E. *p<0.05 sham-control versus nano-TiO₂ at 25 μL/min B) Linear relationship between calculated shear stress and increases in intraluminal flow in coronary arterioles. C) Vasodilation as a function of shear stress. Equations of 1^st-order regression lines are sham-control: y = 2.86× + 53.01, r² = 0.98 and nano-TiO₂, y = −0.85× + 68.49, r² = 0.80. Vasodilation is characterized as % Relaxation. Values are means ± S.E. *p<0.05 sham-control regression line versus nano-TiO₂ regression line.

Figure 3

Endothelium-dependent vasodilation to ACh was decreased in rats exposed to nano-TiO₂ (n = 8) compared to arterioles from sham-control rats (n = 18). Vasodilation is characterized as % Relaxation. Values are means ± S.E. *p<0.05 sham-control versus nano-TiO₂.

Figure 4

Coronary arterioles from rats exposed to nano-TiO₂ (n = 6) display a blunted vasodilation to the highest concentration of A23187 (1×10⁻⁶ M) as compared to sham-control (n = 10). Vasodilation is characterized as % Relaxation. Values are means ± S.E. *p<0.05 sham-control versus nano-TiO₂.

Figure 5

Vasodilation to SNP, an NO donor, was similar between coronary arterioles from rats exposed to nano-TiO₂ (n = 8) and those from sham-control rats (n = 8). Vasodilation is characterized as % Relaxation. Values are means ± S.E.