Depletion of intracellular Ca2+ stores enhances flow‐induced vascular dilatation in rat small mesenteric artery
C Liu, CY Ngai, Y Huang, WH Ko, M Wu… - British journal of …, 2006 - Wiley Online Library
British journal of pharmacology, 2006•Wiley Online Library
The effect of depleting intracellular Ca2+ 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 Ca2+ from …
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 Ca2+ from …
- The effect of depleting intracellular Ca2+ 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 Ca2+ from the intraluminal flow medium.
- Depletion of intracellular Ca2+ 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 Ca2+ influx was also markedly enhanced in arteries pretreated with CPA or BHQ.
- Flow‐induced dilatation was insensitive to Nw‐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 H2O2 (90–220 μM) induced relaxation in phenylephrine‐preconstricted arteries. Relaxation to exogenous H2O2 was blocked in the presence of 30 mM extracellular K+, and H2O2 (90 μM) hyperpolarized the smooth muscle cells, indicating that H2O2 can act as an EDHF.
- In conclusion, flow‐induced dilatation in rat mesenteric arteries can be markedly enhanced by prior depletion of intracellular Ca2+ stores. Furthermore, these data are consistent with a role for H2O2 as the vasodilator involved.
British Journal of Pharmacology (2006) 147, 506–515. doi:10.1038/sj.bjp.0706639
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