Rho kinase and hypertension

Wirth, Angela

doi:10.1016/j.bbadis.2010.05.002

Cited by 107 publications

(105 citation statements)

References 121 publications

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“…The classical Rho kinase signaling involves phosphorylation of myosin phosphatase target subunit 1, which decreases the ability of myosin light chain phosphatase to dephosphorylate myosin light chain, thereby maintaining vascular contractility. 52 However, additional Rho kinase actions have been proposed. Inhibition of Rho kinase by fasudil reverses hypercholesterolemia-induced downregulation of Nrf2-regulated enzymes, such as catalase, glutathione peroxidase, and superoxide dismutase in rats.…”

Section: Figure 2 High Glucose (Hg)-induced Reactive Oxygen Species mentioning

confidence: 99%

Internal Pudental Artery Dysfunction in Diabetes Mellitus Is Mediated by NOX1-Derived ROS-, Nrf2-, and Rho Kinase–Dependent Mechanisms

et al. 2016

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E rectile dysfunction (ED) is characterized by the inability to develop or maintain penile erection during sexual activity.1 In healthy subjects, penile erection depends on highly coordinated responses, involving relaxation of the pre-and intrapenile vasculature, leading to increased penile blood flow, increased intracavernosal pressure, and penile tumescence. 2,3 Arterial blood flow to the corpus cavernosum originates from the internal iliac arteries, courses to the internal pudendal arteries (IPA), and terminates in the bilateral cavernous arteries. Functional and structural changes in the IPA lead to ED. 4 Diabetes mellitus (DM) is an important risk factor for ED. Over 50% of men with DM develop ED. [5][6][7] In humans, DM is associated with stenosis and occlusion of IPA, which can compromise blood inflow to the corpora cavernosa and, consequently, impair erectile function. 8,9 Abnormalities in IPA are found in 36.7% of diabetic patients. 10 Although it may be expected that IPA display DM-associated dysfunction, 11 almost no studies have addressed the function of IPA in DM. 12 Hyperglycemia, hyperlipidemia, and inflammation, 3 main metabolic abnormalities in DM, induce reactive oxygen species (ROS) generation and oxidative stress. Oxidative stress, defined as a disturbance in the production of ROS or in the ability of the antioxidant defenses to neutralize ROS, is critically involved in DM-associated complications, including nephropathy, cardiomyopathy, endothelial dysfunction, and ED. 6,[13][14][15] Nicotinamide adenine dinucleotide phosphate-oxidase (NADPH oxidase) is the main source of ROS in the vasculature. Seven NADPH oxidase isoforms have been identified (NOX1-5, Duox1, Duox2), 16 with nicotinamide adenine dinucleoride phosphate oxidase 1 (NOX1) playing an important role in vascular smooth muscle cell (VSMC) proliferation, migration, and extracellular matrix production.17 IncreasedAbstract-Oxidative stress plays an important role in diabetes mellitus (DM)-associated vascular injury. DM is an important risk factor for erectile dysfunction. Functional and structural changes in internal pudendal arteries (IPA) can lead to erectile dysfunction. We hypothesized that downregulation of nuclear factor E2-related factor 2 (Nrf2), consequent to increased nicotinamide adenine dinucleotide phosphate oxidase 1 (NOX1)-derived reactive oxygen species (ROS), impairs IPA function in DM. IPA and vascular smooth muscle cells from C57BL/6 (control) and NOX1 knockout mice were used. DM was induced by streptozotocin in C57BL/6 mice. Functional properties of IPA were assessed using a myograph, protein expression and peroxiredoxin oxidation by Western blot, RNA expression by polymerase chain reaction, carbonylation by oxyblot assay, ROS generation by lucigenin, nitrotyrosine, and amplex red, and Rho kinase activity and nuclear accumulation of Nrf2 by ELISA. IPA from diabetic mice displayed increased contractions to phenylephrine (control 138.5±9.5 versus DM 191.8±15.5 Nuclear factor E2-related factor 2 (Nrf2) is the mai...

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Section: Figure 2 High Glucose (Hg)-induced Reactive Oxygen Species mentioning

confidence: 99%

Internal Pudental Artery Dysfunction in Diabetes Mellitus Is Mediated by NOX1-Derived ROS-, Nrf2-, and Rho Kinase–Dependent Mechanisms

et al. 2016

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“…V ascular tone of resistance vessels is a function of both calcium entry and calcium sensitization the levels of which are modulated by the activity of endogenous vasoconstrictor and vasodilator systems [1][2][3][4][5]. The role of enhanced calcium entry through L-type voltagedependent calcium channels (L-VDCCs) in genetic hypertension is well known [6][7][8][9], but less attention has been paid to the changes of calcium sensitization (mediated by RhoA/Rho kinase pathway) in spontaneously hypertensive rats (SHRs) [10][11][12].…”

Section: Introductionmentioning

confidence: 99%

Ontogenetic changes in contribution of calcium sensitization and calcium entry to blood pressure maintenance of Wistar–Kyoto and spontaneously hypertensive rats

Behuliak

Vavřínová

Bencze

et al. 2015

Journal of Hypertension

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“…Moreover these patients have decreased phosphorylation of MYPT-1 [71], a marker of Rho kinase activity [44], which conversely is increased in hypertensive patients [71]. Rho kinase, in fact, via an inhibitory phosphorylation of MYPT-1, increases the activity of MLC kinase, leading to smooth muscle contraction and cardiovascular and renal remodeling [72].…”

Section: The Rhoa/rho Kinase/no System Relationshipmentioning

confidence: 99%

Angiotensin II and Cardiovascular-Renal Remodelling in Hypertension: Insights from a Human Model Opposite to Hypertension

Ravarotto

Pagnin

Fragasso

et al. 2015

High Blood Press Cardiovasc Prev

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Insights into the Angiotensin II (Ang II) signalling pathways have been provided by extensive studies using Bartter's/Gitelman's syndromes patients. These syndromes are characterized by activation of the renin-angiotensin-aldosterone system but do not develop hypertension and cardiovascular remodelling, therefore represent a mirror image of hypertension and clinically manifest themselves as the opposite of hypertension. The short and the long-term signalling of Ang II remain an important matter of investigation to shed light on mechanisms responsible for the pathophysiology of hypertension and its long-term complications, such as cardiovascular remodelling and atherogenesis. In particular the long-term signalling of Ang II is involved in the pathophysiology of cardiovascular-renal remodelling, inflammatory and hypertrophic responses in which the relationship between RhoA/Rho kinase pathway and NO system plays a crucial role. This review reports the results of our studies in Bartter's and Gitelman's syndromes to get better insight these processes and the role of Ang II signaling. The information obtained from the studies in Bartter's/Gitelman's patients can, in fact, clarify, confirm or be used to gather more general data on the biochemical mechanisms responsible for the pathophysiology of hypertension and its long-term complications and could contribute to identify additional potential significant targets of therapy.

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Rho kinase and hypertension

Cited by 107 publications

References 121 publications

Internal Pudental Artery Dysfunction in Diabetes Mellitus Is Mediated by NOX1-Derived ROS-, Nrf2-, and Rho Kinase–Dependent Mechanisms

Internal Pudental Artery Dysfunction in Diabetes Mellitus Is Mediated by NOX1-Derived ROS-, Nrf2-, and Rho Kinase–Dependent Mechanisms

Ontogenetic changes in contribution of calcium sensitization and calcium entry to blood pressure maintenance of Wistar–Kyoto and spontaneously hypertensive rats

Angiotensin II and Cardiovascular-Renal Remodelling in Hypertension: Insights from a Human Model Opposite to Hypertension

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