Key result
Olmesartan treatment in hypertensive patients significantly reduced p63RhoGEF levels (1.3 vs 1.0 d.u., p<0.0001) and MYPT-1 phosphorylation (1.2 vs 0.8, p=0.001) at 6 months compared to baseline.
Why the study?
Does olmesartan reduce p63RhoGEF levels and MYPT-1 phosphorylation in untreated hypertensive patients?
Does olmesartan reduce p63RhoGEF levels and MYPT-1 phosphorylation in untreated hypertensive patients?
Absolute Event Rate: 1% vs 1.3%
p-value: p=<0.0001
Olmesartan reduces markers of RhoA/Rho kinase activation in hypertensive patients, providing a mechanistic rationale for its anti-remodeling effects.
Olmesartan-associated RhoA marker reductions support mechanistic hypotheses; leaves open clinical anti-remodeling benefits pending randomized confirmation.
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.
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Ravarotto et al. (2015) studied Hypertension (n=15). Olmesartan vs. Baseline was evaluated on p63RhoGEF protein level (p=<0.0001). Olmesartan treatment in hypertensive patients significantly reduced p63RhoGEF levels (1.3 vs 1.0 d.u., p<0.0001) and MYPT-1 phosphorylation (1.2 vs 0.8, p=0.001) at 6 months compared to baseline.
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