High intravascular pressure decreases endothelial Ca2+ pulsars and impairs endothelium‐dependent vasodilation in mouse mesenteric arteries

Abstract

Ca2+ pulsars are inositol 1,4,5‐triphosphate (IP3) receptor‐mediated Ca2+ events in endothelial cells. Increase in Ca2+ pulsars by acetylcholine (ACh) is associated with endothelium‐dependent vasodilation. The objective of this study was to evaluate the effect of intravascular pressure on Ca2+ pulsars and endothelium dependent vasodilation of resistance arteries. Third‐order mesenteric arteries (MAs) from C57BL6 mice were pressurized at 80 or 120 mmHg and were allowed to develop myogenic tone (26± 1% and 36 ± 1 % at 80 and 120 mmHg respectively, n=9). Endothelium dependent vasodilation to ACh (5 μM) was significantly higher at 80 mmHg compared to 120 mmHg (76.8 ± 7.8 % and 30.1 ± 4.6% respectively, n=4–6, p<0.05). To evaluate the effect of intravascular pressure on Ca2+ pulsars, we used MAs from mice that express a calcium biosensor (GCaMP2) exclusively in endothelial cells. Frequency of Ca2+ pulsars (pulsars/second/site) was higher at 80 mmHg compared to 120 mmHg (0.11 ± 0.01 and 0.07 ± 0.01 respectively, n=15–31 sites). Following ACh treatment, the Ca2+ pulsar frequency increased to 0.19 ± 0.02 at 80 mmHg compared to 0.09 ± 0.01 at 120 mmHg (n=9–10 sites, p<0.05). Taken together, these results indicate that impaired endothelium‐dependent dilation of resistance arteries at high intravascular pressure is associated with a decrease in Ca2+ pulsars in the endothelial cells. Supported by NIH HL44455.