Vascular oxidative stress is associated with insulin resistance in hyper-reninemic nonmodulating essential hypertension.

Background: Nonmodulating hypertension (NMHT) is a high-renin subtype of salt-sensitive hypertension due to renal hemodynamic alterations.

Aims: To evaluate, in NMHT, whether the increased oxidative stress, which interferes with endothelial function, could be the consequence of an elevated renin-angiotensin activity and insulin resistance.

Methods: Fourteen patients with NMHT and 12 with modulating hypertension (MHT) were included. Plasma renin activity (PRA) and glucose/insulin tolerance test were performed and homeostasis model assessment (HOMA) index and areas under the curves (AUC) calculated. Urinary nitrites and nitrates (NOx), urinary cyclic guanosine monophosphate (cGMP) activity, urinary isoprostanes and plasma nitrotyrosine levels were also measured.

Results: PRA was higher in NMHT than MHT. In addition, L-arginine infusion increased effective renal plasma flow in MHT but not in NMHT. Insulin levels were higher in NMHT both at fasting and at 120 min, as were HOMA and AUC values. In MHT, NOx and cGMP significantly increased when moving from low to high Na+ intake, while nitrotyrosine mass and isoprostanes failed to show any change. On the contrary, in NMHT under low Na+ intake, urinary NOx levels were significantly higher than MHT under high Na+ intake, and failed to show any change under high Na intake; cGMP also failed to show any change when patients moved from low to high Na+ intake. Nitrotyrosine mass and isoprostanes, like to NOx, were significantly higher in NMHT under both low and high Na+ intake.

Conclusions: It is suggested that, in NMHT, a possible association between higher renin-angiotensin system activity, insulin resistance and endothelial dysfunction, showed for the first time in the same subjects, might result in systemic vascular and renal endothelial dysfunction, salt-sensitive hypertension and high cardiovascular risk.