Role of the nitric oxide metabolic pathway and prostanoids in the pathogenesis of endothelial dysfunction and essential hypertension in young men

The aim of this study was to explore the role of selected prostanoids and the nitric oxide (NO) metabolic pathway in the pathogenesis of endothelial dysfunction (ED) in young men with and without essential hypertension (HTN). A total of 70 men aged 18-40 years old (23 hypertensive and 47 normotensive) were investigated. Initial metabolite concentrations of the NO pathway (asymmetric dimethylarginine, L-arginine and symmetric dimethylarginine), selected cardiovascular risk markers (serum lipids, creatinine, glucose and high-sensitivity C-reactive protein), oxidative stress markers (malonylodialdehyde, thiol index and nitrotyrosine) and prostanoids (thromboxane B2 (TxB(2)) and 6-keto-prostaglandin F (PGF)-1-α) were measured. Ultrasound assessment of endothelial function (flow-mediated vasodilation (FMD)) of the brachial artery was studied before and after intravenous infusion of L-arginine (16.0 g). All measurements were repeated after oral administration of indomethacin (75 mg per day) for 2 days. The prevalence of ED was similar in both hypertensive and normotensive groups. A lower baseline plasma level of 6-keto-PGF-1-α and a higher baseline of TxB(2) were observed in the hypertensive group. A different response to indomethacin assessed by prostanoid levels was observed and was dependent on the presence of HTN. No significant differences in metabolites of the NO pathway were observed at either baseline or following indomethacin treatment. In hypertensive patients, L-arginine and indomethacin had a synergistic positive effect on FMD. ED in young normotensive men primarily depends on NO deficiency. In young hypertensive men, disorders in prostanoid metabolism have important roles in decreasing NO bioavailability. The high prevalence of ED in potentially healthy subjects suggests that the ultrasound FMD measurement is an important tool in the stratification of cardiovascular risk.