We investigated the effects of antihypertensive treatment with two drug combinations on insulin signalling and oxidative stress.
Twenty essential hypertensive patients were included in the study and treated for 4 weeks with lercanidipine orally. Then they were treated for 6 months with lercanidipine+enalapril (n=10) or lercanidipine+hydrochlorothiazide (n=10). Investigations were performed in basal condition, after 4 weeks of monotherapy with lercanidipine, and at the end of the combination treatment. Insulin signalling was evaluated in mononuclear cells by Wester-Blot. Circulating levels of C-reactive protein (CRP), proinflammatory cytokines interleukin-6 and interleukin-18 (IL-18), macrophage chemotactic factor-1 (MCP-1), soluble vascular cell adhesion molecule 1 and soluble inter-cellular adhesion molecule 1, malonyldialdehyde and lipid peroxidation were measured in plasma.
Results are summarized in the Table (*P<0.05, **p<0.01 vs. Basal; #p<0.05 vs. lercanipine alone). An increased expression of insulin receptor, GLUT-4 and an increased activation of p70S6K1 were observed during treatment with lercanidipine+enalapril but not with lercanidipine+hydrochlorothiazide. A reduction in circulating levels of IL 18, CRP and MCP-1 was observed after treatment with lercanidipine alone, which persisted or further improved after treatment with lercanidipine+enalapril but not with lercanidipine+hydrochlorothiazide.
Therefore the combination treatment lercanidipine+enalapril seems more effective than lercanidipine+hydrochlorothiazide in activating insulin signalling, possibly due to a more marked antioxidant/antiinflammatory effect.