Depletion of intracellular Ca ²⁺ stores enhances flow-induced vascular dilatation in rat small mesenteric artery

The effect of depleting intracellular Ca ²⁺ stores on flow-induced vascular dilatation and the mechanism responsible for the vasodilatation were examined in rat isolated small mesenteric arteries. The arteries were pressurized to 50 mmHg and preconstricted with phenylephrine. Intraluminal flow reversed the effect of phenylephrine, resulting in vasodilatation. Flow dilatation consisted of an initial transient peak followed by a sustained plateau phase. The magnitude of dilatation was markedly reduced by removing Ca ²⁺ from the intraluminal flow medium. Depletion of intracellular Ca ²⁺ stores with either cyclopiazonic acid (CPA, 2 μM) or 1,4-dihydroxy-2,5-di-tert-butylbenzene (BHQ, 10 μM) significantly augmented the magnitude of flow dilatation. Flow-induced endothelial cell Ca ²⁺ influx was also markedly enhanced in arteries pretreated with CPA or BHQ. Flow-induced dilatation was insensitive to N ^w-nitro-L- arginine methyl ester (100 μM) plus indomethacin (3 μM) or to oxyhemoglobin (3 μM), but was markedly reduced by 30 mM extracellular K ⁺ or 2 mM tetrabutylammonium (TBA), suggesting an involvement of EDHF. Catalase at 1200 U ml ^-1 abolished the flow-induced dilatation, while the application of exogenous H ₂O ₂ (90-220 μM) induced relaxation in phenylephrine-preconstricted arteries. Relaxation to exogenous H ₂O ₂ was blocked in the presence of 30 mM extracellular K ⁺, and H ₂O ₂ (90 μM) hyperpolarized the smooth muscle cells, indicating that H ₂O ₂ can act as an EDHF. In conclusion, flow-induced dilatation in rat mesenteric arteries can be markedly enhanced by prior depletion of intracellular Ca ²⁺ stores. Furthermore, these data are consistent with a role for H ₂O ₂ as the vasodilator involved. © 2006 Nature Publishing Group All rights reserved.