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A new ATP-sensitive potassium channel opener protects endothelial function in cultured aortic endothelial cells


, : A new ATP-sensitive potassium channel opener protects endothelial function in cultured aortic endothelial cells. Cardiovascular Research 73(3): 497-503

Objective: Endothelial dysfunction is an early risk factor for cardiovascular disease and hypertension. Mechanisms that participate in endothelial dysfunction include reduced nitric oxide (NO) generation and increased endothelin-1 (ET-1) generation. Endothelial ATP-sensitive potassium (K-ATP) channels are responsible for maintaining the resting potential of endothelial cells and modulating the release of vasoactive compounds. We hypothesized that activation of endothelial K-ATP channels might result in the protection against endothelial dysfunction.Methods: Using cultured bovine or rat aortic endothelial cells, we examined the effects of a new K-ATP channels opener, iptakalim, on the secretion of vasoactive substances. We also investigated its effects on the expression of adhesion molecules in metabolically disturbed cultured endothelial cells.Results: In cultured aortic endothelial cells, iptakalim caused a concentration-dependent inhibition of ET-1 release and synthesis that correlated with reduced levels of mRNA for ET-1 and endothelin-converting enzyme. These effects of iptakalim were significantly inhibited by pretreatment with glibenclamide (a K-ATP channel blocker) for 1 h. Similarly, iptakalim enhanced the release of NO in a concentration-dependent manner and increased basal levels of free intracellular calcium. Iptakalim at the concentrations of 100 and 1000 mu M increased the activities of NO synthase (NOS) significantly. After the activity of NOS was blocked by L-N-omega-nitro-arginine methyl ester (L-NAME), the inhibition of iptakalim on ET-1 release was abolished. In endothelial cell models of metabolic disturbance induced by low-density lipoprotein, homocysteine, or hyperglycemia, treatment with iptakalim could inhibit the overexpression of monocyte chemoattractant protein-1 (MCP-1), Intercellular adhesive molecule-1 (ICAM-1), and vascular cell adhesive molecule-1 (VCAM-1) mRNA.Conclusion: Iptakalim is a promising drug that could protect against endothelial dysfunction through activating K-ATP channels in endothelial cells.

US$19.90

PMID: 17116295

DOI: 10.1016/j.cardiores.2006.10.007


Other references

Large, M.F.; Braggins, J.E., 1993: A morphological assessment of Adiantum hispidulum Swartz and A. pubescens Schkuhr (Adiantaceae: Filicales) in New Zealand. Two polymorphic members of the Adiantum hispidulum Swartz complex, A. hispidulum sensu stricto and A. pubescens Schkuhr, have been critically studied on a morphological basis, utilising frond and hair forms, pinnule shape and size, soral features,...

Barta, O., 1961: The organization and results of preventive orthopedic examination in the Vas region. Nepegeszsegugy 42: 147-150

Umiker, W., 1993: Coping with employee departures. Resignations should be treated as minicrises. The highly structured procedure for handling employee exists described in this article can be effective in reducing employee turnover problems. Employees are recipients of your supervisory service, and...

Kashiwabara, T.; Kondo, K., 1954: The effect of X-ray irradiation on the spermatogenesis of the mouse. III.. Permanent sterility resulted from a 1000 r level of local radiation; temporary sterility was caused by 500-1000 r. The minimum dose to influence spermatogenesis was 250 r. There was a relationship between the amount of damage caused and the durati...

Bolen, J.B., 1991: Signal transduction by the SRC family of tyrosine protein kinases in hemopoietic cells. Cell Growth & Differentiation 2(8): 409-414

Weil, M.; Borel, C.; Auclerc, G.; Petit, T.; Rixe, O.; Thomas, A.; Kolodziejska, E.; Nizri, D.; Baillet, F.; Soubrane, C.; Khayat, D., 1996: Mature results in 477 breast cancer patients treated by neoadjuvant chemotherapy and exclusive radiotherapy. Breast Cancer Research & Treatment 37(SUPPL ): 92

Murphy J.S., 1973: The death rate of lysogenic bacteria after uv induction follows gompertzs law. Mechanisms of Ageing & Development 2(2): 125-139

Stiles, B.F.; Hendrickson, G.O., 1946: Ten years of roadside pheasant censuses in Iowa. Roadside pheasant census in 33 Iowa counties, 1936[long dash]45, has been fairly successful in helping authorities establish open seasons, closed seasons, bag limits, possession limits, and territorial limitations. Roadside counts were followed by...

Bibinova, L.S.; Kruglikhina, Z.M.; Nikulnikova, N.S., 1971: Morphological changes induced in the guinea pig intestinal tract by enterally administered dysentery endotoxin. Journal of Hygiene, Epidemiology, Microbiology, and Immunology 15(2): 212-219

Fiser, R.H.; Phelps, D.L.; Williams, P.R.; Sperling, M.A.; Fisher, D.A.; Oh, W., 1974: Insulin-glucagon substrate interrelationships in the neonatal sheep. American Journal of Obstetrics and Gynecology 120(7): 944-950