Effect of direct renin inhibition on vascular function after long-term treatment with aliskiren in hypertensive and diabetic patients

We tested the hypothesis that chronic treatment with the direct renin inhibitor aliskiren improves
vascular function in resistance and conduit arteries of type 2 diabetic and hypertensive patients.
Sixteen patients with mild essential hypertension and with a previous diagnosis of non–insulindependent
diabetes mellitus were included in the study. Patients were then randomized to aliskiren
(150 mg once daily, n=9), or ramipril (5 mg once daily, n=7). Each patient underwent a biopsy of
the subcutaneous tissue and small arteries were dissected and mounted on a pressurized
micromyograph in order to evaluate endothelium dependent vasorelaxation in response to
acetylcholine  L-NAME in vessels precontracted with norepinephrine. Endothelial function has
been quantified also in large conduit arteries by Flow Mediated Dilation (FMD). A similar office
blood pressure–lowering effect was observed with the 2 drugs, although changes in diastolic blood
pressure were not statistically significant in the ramipril group. Aliskiren significantly improved
endothelium-dependent relaxation in subcutaneous resistance arteries, as well as increased FMD in
conduit arteries, whereas the effects induced by ramipril did not reach statistical significance. Only
aliskiren significantly increased the expression of p1177-eNOS in the endothelium. Both aliskiren
and ramipril had a negligible effect on markers of oxidative stress. Thus aliskiren restored
endothelial function and induced a more prompt peripheral vasodilation in hypertensive and
diabetic patients possibly through the increased production of NO via the enhanced expression and
function of the active phosphorylated form of eNOS.