Korean Circ J.  2004 Jun;34(6):600-609. 10.4070/kcj.2004.34.6.600.

Nitric Oxide-Induced Intracellular Ca2+ Modulation in Macrovascular Endothelial Cells

• Jeon SH
• Seol GH
• Suh SH
• Park SH

• KMID: 1858910
• DOI: http://doi.org/10.4070/kcj.2004.34.6.600

Abstract

BACKGROUND AND OBJECTIVES
Nitric oxide (NO) reduces the intracellular Ca2+ concentration ([Ca2+]i) in smooth muscle cells, whereas the effect of NO on [Ca2+]i in endothelial cells is still controversial. Therefore, the effect of NO on the [Ca2+]i, and its mechanism in mouse aortic endothelial cells (MAEC) and human umbilical vein endothelial cells (HUVEC) were examined.
MATERIALS AND METHODS
In primary cultured MAEC and HUVEC, cells were loaded with fura 2-AM and [Ca2+]i and measured using a microfluorometer.
RESULTS
The NO donor, sodium nitroprusside (SNP), reduced the [Ca2+]i in 72% of the cells tested (n=100). In the remaining cells, the effect of SNP was biphasic, or the [Ca2+]i was increased. In addition, the membrane-permeable cGMP, 8-bromo cGMP, decreased the [Ca2+]i. The effects of SNP and 8-bromo cGMP were inhibited by the soluble guanylate cyclase inhibitor, 1H-[1,2,4] oxadiazole[4,3-a]quinoxalin-1-one (ODQ), and the cGMP-dependent protein kinase inhibitor, KT5823, respectively. In contrast, in the presence of 8-bromo cGMP or ODQ, SNP increased the [Ca2+]i.
CONCLUSION
These results suggest that NO inhibits the [Ca2+]i through a cGMP-dependent mechanism and increases the [Ca2+]i through a cGMP-independent mechanism.

Keyword

Endothelium; Intracellular calcium; Cyclic GMP; Nitric oxide

MeSH Terms

Animals
Cyclic GMP
Endothelial Cells*
Endothelium
Guanylate Cyclase
Human Umbilical Vein Endothelial Cells
Humans
Mice
Myocytes, Smooth Muscle
Nitric Oxide
Nitroprusside
Protein Kinases
Tissue Donors
Cyclic GMP
Guanylate Cyclase
Nitric Oxide
Nitroprusside
Protein Kinases