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
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 remode...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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SAGE Publications
2015-12-01
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| Series: | Journal of the Renin-Angiotensin-Aldosterone System |
| Online Access: | https://doi.org/10.1177/1470320315594324 |
| _version_ | 1797285447179698176 |
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| author | Verdiana Ravarotto Elisa Pagnin Giuseppe Maiolino Antonio Fragasso Gianni Carraro Barbara Rossi Lorenzo A Calò |
| author_facet | Verdiana Ravarotto Elisa Pagnin Giuseppe Maiolino Antonio Fragasso Gianni Carraro Barbara Rossi Lorenzo A Calò |
| author_sort | Verdiana Ravarotto |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-07T18:03:17Z |
| format | Article |
| id | doaj.art-1c395666ca3b4d778c9ceb11185c88b0 |
| institution | Directory Open Access Journal |
| issn | 1470-3203 1752-8976 |
| language | English |
| last_indexed | 2024-03-07T18:03:17Z |
| publishDate | 2015-12-01 |
| publisher | SAGE Publications |
| record_format | Article |
| series | Journal of the Renin-Angiotensin-Aldosterone System |
| spelling | doaj.art-1c395666ca3b4d778c9ceb11185c88b02024-03-02T10:10:42ZengSAGE PublicationsJournal of the Renin-Angiotensin-Aldosterone System1470-32031752-89762015-12-011610.1177/1470320315594324The blocking of angiotensin II type 1 receptor and RhoA/Rho kinase activity in hypertensive patients: Effect of olmesartan medoxomil and implication with cardiovascular-renal remodelingVerdiana Ravarotto0Elisa Pagnin1Giuseppe Maiolino2Antonio Fragasso3Gianni Carraro4Barbara Rossi5Lorenzo A Calò6Hypertension Clinic, University of Padova-Azienda Ospedaliera Padova, ItalyDepartment of Medicine Nephrology, University of Padova-Azienda Ospedaliera Padova, ItalyHypertension Clinic, University of Padova-Azienda Ospedaliera Padova, ItalyDepartment of Medicine Nephrology, University of Padova-Azienda Ospedaliera Padova, ItalyDepartment of Medicine Nephrology, University of Padova-Azienda Ospedaliera Padova, ItalyDepartment of Medicine Nephrology, University of Padova-Azienda Ospedaliera Padova, ItalyDepartment of Medicine Nephrology, University of Padova-Azienda Ospedaliera Padova, ItalyHypothesis/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.https://doi.org/10.1177/1470320315594324 |
| spellingShingle | Verdiana Ravarotto Elisa Pagnin Giuseppe Maiolino Antonio Fragasso Gianni Carraro Barbara Rossi Lorenzo A Calò 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 Journal of the Renin-Angiotensin-Aldosterone System |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| url | https://doi.org/10.1177/1470320315594324 |
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