Endothelial dysfunction, nitric oxide and platelet activation in hypertensive and diabetic type II patients.

Alterations in the synthesis or enhanced inactivation of nitric oxide (NO) and an increase in endothelin-1 production lead to an imbalance that can induce arterial hypertension. Type II diabetes is characterized by impaired endothelium-dependent vasodilation and vascular disease. NO is produced through L-arginine pathway by three different isoforms of nitric oxide synthase (NOS), an inducible form that can be activated by cytokines such as tumor necrosis factor alpha (TNFalpha). We evaluated NO plasmatic levels, endothelial damage markers such as von Willebrand factor (vWF), platelet activation, soluble P-selectin (sP-Sel), TNFalpha levels, insulinaemia (I), glycosylated haemoglobin (HbA1c), glycaemia and blood pressure in 32 hypertensive diabetic type II patients (Group A), 37 hypertensive patients (Group B) and 35 healthy subjects (Group C) matched in sex, age, body mass index and dietary habits. The level of I was increased in patients compared to the controls and correlated with their NO levels. vWF plasmatic levels were increased in Group A compared to Groups B and C. We also found significant differences in platelet activation among all the groups. In diabetic patients, increased NO levels correlated with TNFalpha, HbA1c and platelet activation showed greater endothelial damage than in Group B. These parameters described a prothrombotic state associated with an insulin resistance state, an increased vWF release, raised sP-Sel and TNFalpha levels and, maybe, low NO bioavailability, which could lead to a higher risk of development of thrombotic events in hypertensive diabetic patients (Group A) than in the hypertensive patients in Group B.

Nitric oxide in liver transplantation.

Liver transplantation is the only therapeutic option for patients with end-stage liver disease. Nitric oxide, a free radical produced from L-arginine, a potent vasodilator, also inhibits platelet adhesion and aggregation, reduces adhesion of leukocytes to the endothelium and suppresses proliferation of vascular smooth muscle cells. The inducible form of the nitric oxide synthase may generate large quantities of nitric oxide, and may be induced by the action of cytokines and lipopolysaccharides. Nitric oxide can be released from the hepatic vascular endothelium, platelets and Kupffer cells as a response to ischemia-reperfusion injury and circulatory shock. We analyzed the relationships between the levels of nitric oxide, hepatic enzymes and other clinical parameters (glucose, total proteins, total bilirubin, creatinine, albumin) obtained in serum samples before liver transplantation and every 48 h till day 15 in 15 patients aged 40 +/- 13 years. Aspartate aminotransferase and alanine aminotransferase levels changed from high at the beginning, to almost normal at the end of the study, cholinesterase levels remained decreased throughout the study and nitric oxide remained high, never reaching normal values.

Hemolytic uremic syndrome in children: platelet aggregation and membrane glycoproteins.

PURPOSE: Several mechanisms have been proposed to explain the fibrin-platelet thrombosis at the microcirculation level in the different clinical conditions of hemolytic uremic syndrome (HUS). The relationships between platelet structure and function during the first 4 weeks of evolution of the disease were studied to understand the mechanism of platelet alteration. PATIENTS AND METHODS: Coagulation parameters, platelet counts, and aggregation were studied in 49 children, and membrane glycoproteins (GPs) in 20 of the 49 children (mean age, 17 months) with HUS (Group 2) were studied during the first 4 weeks of evolution of the disease. RESULTS: No disseminated intravascular coagulation was found in patients with recurrent or persistent thrombocytopenia. Platelet aggregation was sequentially performed during the first weeks of evolution. All patients had a functional decrease in the acute period of HUS. Platelet GPs GPIb, GPIIbIIIa, GPIIb, and GPIIIa were evaluated. GPIIbIIIa complex presented low level and never reached normal values during the first 4 weeks of disease. CONCLUSIONS: Platelet alterations are probably caused by multiple mechanisms: "exhausted" platelets, structural membrane alterations caused by arginine-glycine-aspartic peptide blockade, or diminished or nonfunctional membrane GPIb and GPIIbIIIa complexes.