Plasma nitrate levels and flow-mediated vasodilation in untreated major depression.

OBJECTIVE: Findings from several studies have revealed that major depression is associated with an increased cardiovascular risk. The physiopathologic mechanisms of this association remain unclear, although recently, it has been hypothesized that a decreased production of nitric oxide could be a potential contributor to vascular dysfunction in depressive patients. The objective of this study was to evaluate nitric oxide production and vascular endothelial function in treatment-naive young healthy adults with a first episode of major depression. METHODS: A case-control study in 50 treatment-naive young adults with a first episode of major depression and 50 healthy control subjects was conducted. Plasma levels of nitric oxide metabolites (nitrates/nitrites) were determined using a colorimetric assay based on Griess reaction. Endothelial function was assessed by flow-mediated vasodilation measurements after reactive hyperemia. RESULTS: The mean age of the depressed patients was 22.6 (standard deviation [SD], 4.6) years, whereas the controls were 23.4 (SD, 4.8) years. Sixteen men (32%) and 34 women (68%) were included in each group. The plasma nitrite/nitrate concentrations were significantly lower in depressive subjects compared with healthy controls (17.5 [SD, 4.9] µmol/L versus 21.6 [SD, 7.0] µmol/L, p < .001); however, flow-mediated vasodilation values were similar in both groups (13.1% [SD, 4.3%] versus 12.1% [SD, 5.0%], p = .10). CONCLUSIONS: Decreased plasma concentrations of nitric oxide metabolites are not associated with vascular endothelial dysfunction in young subjects with a first episode of major depression. Reduced nitrate/nitrite levels could reflect a decreased nitric oxide production in the central nervous system of depressed subjects. Further studies are needed to confirm this hypothesis.

Hyperinsulinemia is a predictor of new cardiovascular events in Colombian patients with a first myocardial infarction.

BACKGROUND: Acute Myocardial Infarction (AMI) is one of the main causes of mortality and disability in Colombia. The factors associated to a new event in surviving subjects to a first AMI in our population have not yet been fully identified. METHODS: Two hundred and ninety five surviving subjects to a first AMI (58.8±12.6 years) were included in a prospective cohort study between 2000 and 2006. Lipid profile, glycemia and plasma insulin levels were measured. Deaths of cardiovascular origin, a new AMI, unstable angina, heart failure, stroke, new myocardial revascularization or angioplasty were considered new cardiovascular events. RESULTS: The study included 61 (20.6%) women and 234 (79.4%) men. The mean follow up time was 50±30 months with a 38.9% incidence of new events. Fifty five patients (18.6%) were diabetic. Bi-varied analysis identified as risk factors for a new cardiovascular event the presence of: hypertension, anterior descending coronary artery stenosis, intrahospital cardiac failure, age over 55, low income, lack of education, Killip III-IV, heart rate over 76 bpm, pulse pressure over 80 mmHg, total cholesterol over 200 mg/dl and insulin over 10 IU/ml. After logistic regression analysis, the log values of insulin remained as the only significant predictor for new cardiovascular events. CONCLUSIONS: Hyperinsulinism was the most important factor associated to the occurrence of new cardiovascular events in Colombian patients with AMI, which emphasizes the pivotal role of insulin resistance in the physiopathologic mechanisms of atherosclerosis, especially in undeveloped countries.

The role of the L-arginine-nitric oxide pathway in preeclampsia.

Preeclampsia (PE) is a major cause of maternal and perinatal mortality, especially in developing countries. Its etiology involves multiple factors, but no specific cause has been identified. Evidence suggests that clinical manifestations are caused by endothelial dysfunction. Nitric oxide (NO), which is synthesized from L-arginine in endothelial cells by the endothelial nitric oxide synthase (eNOS), provides a tonic dilator tone and regulates the adhesion of white blood cells and platelet aggregation. Alterations in the L-arginine-NO pathway have been associated with the development of PE. Various studies, reporting decreased, elevated or unchanged levels of nitrite (NO(2)) and nitrate (NO(3)), two end products of NO metabolism, have been published. Our group contributed to those contradictory reports describing cases of PE with both elevated and decreased levels of NO(2) and NO(3). Apparently, diminished levels of NO could be related to deficiencies in the ingestion of dietary calcium associated to low levels of plasma ionic calcium, which is crucial to the eNOS' activity. Also, low levels of NO could be associated with the presence of eNOS polymorphisms or the presence of increased levels of ADMA, the endogenous inhibitor of NO. High levels of NO associated to low levels of cGMP suggest a decreased bioactivity of NO, which is probably related to an increased degradation of NO caused by a high production of superoxide in states of infection and inflammation. The present article analyses and reviews the reported paradoxical roles of the L-arginine-NO pathway in PE and gives a possible explanation for these results.