A spoonful of sugar helps the medicine go down… but platelet eNOS activity go up!

• References

• 1 Radomski M. et al. An L-arginine/nitric oxide pathway in human platelets regulates aggregation. Proc Natl Acad Sci USA 1990; 87: 5193-7.
• 2 Freedman JE. et al. Deficient platelet-derived nitric oxide and enhanced hemostasis in mice lacking the NOSIII gene. Circ Res 1999; 84: 1416-21.
• 3 Massucco P, Mattiello L, Russo I. et al. High glucose rapidly activates the nitric oxide/cyclic nucleotide pathway in human platelets via an osmotic mechanism. Thromb Haemost 2005; 93: 517-26.
• 4 Freedman JE. α -Tocopherol and protein kinase C inhibition enhance platelet-derived nitric oxide release. FASEB J 2000; 14: 2377-9.
• 5 Assert R. et al. Regulation of protein kinase C by short term hyperglycaemia in human platelets in vivo and in vitro. Diabetologia 2001; 44: 188-95.
• 6 Nolte C. et al. Synergistic phosphorylation of the focal adhesion-associated vasodilator-stimulated phosphoprotein in intact human platelets in response to cGMP-and cAMP-elevating platelet inhibitors. Biochem Pharmacol 1994; 48: 1569-75.
• 7 Manns JM, Brenna KJ, Colman RW. et al. Differential regulation of human platelet responses by cGMP inhibited and stimulated cAMP phosphodiesterases. Thromb Haemost 2002; 87: 873-9.
• 8 Fleming I, Busse R. Molecular mechanisms involved in the regulation of the endothelial nitric oxide synthase. Am J Physiol Regul Integr Comp Physiol 2003; 284: R1-R12.
• 9 Guzik TJ. et al. Mechanisms of increased vascular superoxide production in human diabetes mellitus: role of NAD(P)H oxidase and endothelial nitric oxide synthase. Circulation 2002; 105: 1656-62.
• 10 Hirata K, Kuroda R, Sakoda T. et al. Inhibition of endothelial nitric oxide synthase activity by protein kinase C. Hypertension 1995; 25: 180-5.
• 11 Tsukahara H. et al. Continuous monitoring of nitric oxide release from human umbilical vein endothelial cells. Biochem Biophys Res Commun 1993; 193: 722
• 12 Davda RK, Chandler LJ, Guzman NJ. Protein kinase C modulates receptor-independent activation of endothelial nitric oxide synthase. Eur J Pharmacol 1994; 266: 237-44.
• 13 Ayajiki K. et al. Intracellular pH and tyrosine phosphorylation but not calcium determine shear stress-induced nitric oxide production in native endothelial cells. Circ Res 1996; 78: 750-8.
• 14 Harris MB, Ju H, Venema VJ. et al. Reciprocal phosphorylation and regulation of the endothelial nitric oxide synthase in response to bradykinin stimulation. J Biol Chem 2001; 19: 16587-91.
• 15 Fleming I. et al. Phosphorylation of Thr495 regulates Ca2+/calmodulin-dependent endothelial nitric oxide synthase activity. Circ Res 2001; 88: e68-e75.
• 16 Michell BJ. et al. Coordinated control of endothelial nitric-oxide synthase phosphorylation by protein kinase C and the cAMP-dependent protein kinase. J Biol Chem 2001; 276: 17625-8.
• 17 Lenasi H, Kohlstedt K, Fichtlscherer B. et al. Amlodipine activates the endothelial nitric oxide synthase by altering phosphorylation on Ser1177 and Thr495. Cardiovasc Res 2003; 59: 844-53.
• 18 Laight DW, Kaw AV, Carrier MJ. et al. Pharmacological modulation of endothelial function by insulin in the rat aorta. J Pharm Pharmacol 1998; 50: 1117-20.
• 19 Lembo G. et al. Insulin enhances endothelial α 2-adrenergic vasorelaxation by a pertussis toxin mechanism. Hypertension 1997; 30: 1128-34.
• 20 Fleming I, Schulz C, Fichtlscherer B. et al. AMPactivated protein kinase (AMPK) regulates the insulininduced activation of the nitric oxide synthase in human platelets. Thromb Haemost 2003; 90: 863-7.
• 21 Randriamboavonjy V, Schrader J, Busse R. et al. Insulin induces the release of vasodilator compounds from platelets by a nitric oxide-G kinase-VAMP-3-dependent pathway. J Exp Med 2004; 199: 347-56.
• 22 Lantoine F, Brunnet A, Bedioui F. et al. Direct measurement of nitric oxide production in platelets: relationship with cytosolic Ca2+ concentration. Biochem Biophys Res Commun 1995; 215: 842-8.
• 23 Rosado JA, Sage SO. Protein kinase C activates non-capacitative calcium entry in human platelets. J Physiol 2000; 529: 159-69.
• 24 Li Z, Xi X, Gu M. et al. A stimulatory role for cGMP-dependent protein kinase in platelet activation. Cell 2003; 112: 77-86.
• 25 Li Z, Zhang G, Marjanovic JA. et al. A platelet secretion pathway mediated by cGMP-dependent protein kinase. J Biol Chem 2004; 279: 42469-75.
• 26 Keating FK, Sobel BE, Schneider DJ. Effects of increased concentrations of glucose on platelet reactivity in healthy subjects and in patients with and without diabetes mellitus. Am J Cardiol 2003; 92: 1362-5.
• 27 Anfossi G, Russo I, Massucco P. et al. Impaired synthesis and action of antiaggregating cyclic nucleotides in platelets from obese subjects: possible role in platelet hyperactivation in obesity. Eur J Clin Invest 2004; 34: 482-9.
• 28 Touyz RM, Schiffrin EL. Blunted inhibition by insulin of agonist-stimulated calcium, pH and aggregatory responses in platelets from hypertensive patients. J Hypertens 1994; 12: 1255-63.