Combined aliskiren and L‐arginine treatment prevents vascular dysfunction in renovascular hypertension.

Abstract

We investigate aliskiren, L‐arginine and both treatments on vascular reactivity in aortic rings. Hypertension was induced by clipping renal artery and animals were divided: Sham, 2‐kidney, 1‐clip (2K1C), 2K1C+aliskiren (ALSK), 2K1C+L‐arginine (L‐arg), and 2K1C+aliskiren and L‐arginine (ALSK+L‐arg) treatment for 4 weeks. Blood pressure was monitored and endothelium‐dependent and independent vasoconstriction and relaxation were assessed. ALSK+L‐arg decreased blood pressure, contractile response to phenylephrine and improved the acetylcholine relaxation. Endothelium removal and incubation with L‐NAME increased the response to phenylephrine in all groups, but magnitude was higher in ALSK+L‐arg group. Enalapril reduced phenylephrine response in 2K1C and ALSK groups and Losartan reduced in all of the groups. Apocynin reduced contractile response in 2K1C, ALSK and ALSK+L‐arg groups and incubation with superoxide dismutase reduced the response in 2K1C and ALSK groups. eNOS expression increase in 2K1C and L‐arg groups and iNOS increased only in 2K1C group compared with other groups. AT1 expression increase in 2K1C compared to Sham, ALSK and ALSK+L‐arg groups, AT2 expression increase in ALSK+L‐arg group compared to Sham and L‐arg groups, SOD2 increased in ALSK+L‐arg group compared to 2R1C, ALSK and L‐arg group, on the other hand, gp91phox decreased in ALSK+L‐arg compared with 2K1C and ALSK. In conclusion, combined ALSK+L‐arg was effective in preventing endothelial dysfunction of 2K1C hypertensive rats and the mechanisms responsible appear to be related to the modulation of local renin‐angiotensin system, which is associated with the reduction in endothelial oxidative stress.