Insights into the Vasodilation of Rat Retinal Vessels Evoked by Vascular Endothelial Growth Factor121 (VEGF121)
We have previously reported that cultured retinal capillary endothelial cells express VEGFR-2, whereas VEGFR-1 protein could not be detected (Hasséssian, 1997). Both types of VEGF receptor are tyrosine kinases (Ferrara and Davis-Smyth, 1997). Furthermore, we have demonstrated that VEGF121 is more potent than VEGF?65 to evoke vasodilation in the retina, and that the VEGF121 evoked vasodilation is due to the release of nitric oxide (NO) as well as prostacyclin from the endothelium (Hasséssian et al, 1998). Concurrent with the vasodilator effect, we observed increases of intracellular Ca2+, in endothelial cells, which were almost entirely due to influx across the plasma membrane (Hasséssian, 1997). Both VEGF?65 and VEGF12? were found to evoke Ca2+ influx (Hasséssian, 1997). We initiated the current set of experiments to determine if the Ca2+ influx is necessary for the vasodilator response to VEGF121 and to investigate further the cellular mechanisms responsible for the vasodilation.
KeywordsEpoxy Heparin Retina Prostaglandin Gadolinium
Unable to display preview. Download preview PDF.
- Fernando, K.C. and G.J. Barritt, Characterisation of the Inhibition of the Hepatocyte Receptor-Activated Ca2+ Inflow System by Gadolinium and SK&F969365, Biochim Biophys Acta, 1994.Google Scholar
- Galli, C, Meucci O., Scorziello A., Werge, T.M., Calissano, P. and G. Schettmi, Apoptosis in Cerebellar Granule Cells is Blocked by High KC1, Forskolm, and IGF-1 through Distinct Mechanisms of Action: The Involvement of Intracellular calcium and RNA Synthesis, J. Neurosci. 15:1172–1179, 1995.PubMedGoogle Scholar
- Hasséssian H., The Mechanism of Ca2+ Influx Evoked by VEGF Acting on Bovine Retinal Capillary Endothelial Cells, Proceedings of the NATO Advanced Studies Institute, Angiogenesis: Models, Modulators and Clinical Applications, 1997.Google Scholar
- Hasséssian H., El-Dwairi Q., Abran, D.A. Belgaçd, N., Kazanjian, A. and S. Chemtob, Differential Effects of VEGF165 and VEGF12? on the Nitric Oxide System of Retinal Vascular Endothelial Cells, Investigative Ophthalmology and Visual Science (ARVO) Abs #4230, 1998.Google Scholar
- Li X., Zarinetchi F., Schrier, R.W. and R.A., Nemenoff, Inhibition of MAP Kinase by Prostaglandin E2 and Forskolin in Rat Renal Mesangial Cells, Am. J. Physiol. 269:C986–991, 1995.Google Scholar
- Moss J. and M., Vaughan, Activation of Cholera Toxin by ADP-ribosylation Factors, 20-kDa Guanine Nucleotide-Binding Proteins, Curr. Top. Cell Regul. 32:49–72, 1992.Google Scholar
- Nilius, B, Ion Channels in Nonexcitable Cells. In: Cell Physiology, Edited by Nicholas Sperelakis, Academic Press, 1995.Google Scholar