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J Renin Angiotensin Aldosterone Syst. 2015 Dec;16(4):1245-50. doi: 10.1177/1470320315594324. Epub 2015 Aug 3.

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.

Author information

1
Department of Medicine Nephrology, University of Padova-Azienda Ospedaliera Padova, Italy Hypertension Clinic, University of Padova-Azienda Ospedaliera Padova, Italy.
2
Department of Medicine Nephrology, University of Padova-Azienda Ospedaliera Padova, Italy.
3
Hypertension Clinic, University of Padova-Azienda Ospedaliera Padova, Italy.
4
Department of Medicine Nephrology, University of Padova-Azienda Ospedaliera Padova, Italy renzcalo@unipd.it.

Abstract

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.

KEYWORDS:

Rho kinase; angiotensin II signaling; cardiovascular-renal remodeling; hypertension; olmesartan

PMID:
26240115
DOI:
10.1177/1470320315594324
[Indexed for MEDLINE]

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