The blocking of angiotensin II type 1 receptor and RhoA/Rho kinase activity in hypertensive patients: Effect of olmesartan medoxomil and implication with cardiovascular-renal remodeling

• Main Authors: Verdiana Ravarotto, Elisa Pagnin, Giuseppe Maiolino, Antonio Fragasso, Gianni Carraro, Barbara Rossi, Lorenzo A Calò
• Format: Article
• Language: English
• Published: Hindawi - SAGE Publishing 2015-12-01
• Series: Journal of the Renin-Angiotensin-Aldosterone System
• Online Access: https://doi.org/10.1177/1470320315594324

Hypothesis/Introduction: The pathophysiological role of oxidative stress (OxSt) in hypertension and target organ damage is recognized. Angiotensin II (Ang II) induces OxSt via NAD(P)H oxidase activation and production of proinflammatory cytokines/growth factors leading to cardiovascular-renal remodeling. Ang II stimulates the RhoA/Rho kinase (ROCK) pathway, which is deeply involved in the development of cardiovascular-renal remodeling via OxSt induction. Olmesartan, an Ang II type 1 receptor blocker, possesses antioxidant and activating nitric oxide system-related effects, which we have shown in terms of p22 phox reduction, heme oxygenase-1 and calcitonin gene-related peptide increase. This study evaluates in 15 untreated hypertensive patients the effect of olmesartan treatment on p63RhoGEF, key in Ang II-induced ROCK activation, and MYPT-1 phosphorylation, a marker of ROCK activity. Materials and methods: The p63RhoGEF protein level and MYPT-1 phosphorylation (Western blot) were evaluated at baseline, and after three and six months of olmesartan treatment. Results: Olmesartan normalized systolic and diastolic BP ( p < 0.001), reduced p63RhoGEF level: 1.3±0.25 d.u. (baseline) vs 1.0±0.29 (three months), p < 0.0001 vs 1.0±0.22, (six months), p < 0.0001 and MYPT-1 phosphorylation: 1.2 ±0.14 (baseline) vs 0.9±0.19 (three months), p = 0.008, vs 0.8±0.16 (six months), p = 0.001. Conclusions: These data added to our previous results further provide a mechanistic rationale for olmesartan’s antioxidant/anti-inflammatory potential translation, in the long term, toward anti-atherosclerotic/anti-remodeling effects reported by clinical trials.