Vasomodulatory effect of novel peroxovanadate compounds on rat aorta: Role of rho kinase and nitric oxide/cGMP pathway

Published on Sep 1, 2011in Pharmacological Research5.574
· DOI :10.1016/j.phrs.2011.03.016
Vivek Khanna8
Estimated H-index: 8
(Central Drug Research Institute),
Manish Jain14
Estimated H-index: 14
(Central Drug Research Institute)
+ 6 AuthorsMadhu Dikshit34
Estimated H-index: 34
(Central Drug Research Institute)
Abstract The present study was undertaken to assess the role of reactive oxygen species (ROS) in rat aortic ring vasoreactivity and integrity by using various peroxovanadate (pV) compounds. All the pV compounds (1 nM–300 μM) used in the present study exerted concentration-dependent contractions on endothelium intact rat aortic rings. All compounds with an exception of DPV-asparagine (DPV-asn) significantly altered vascular integrity as shown by diminished KCl responses. Phenylephrine (PE)-mediated contractions (3 nM–300 μM) were unaltered in the presence of these compounds. Acetylcholine (Ach)-mediated relaxation in PE (1 μM) pre-contracted rings was significantly reduced in presence of diperoxovanadate (DPV), poly (sodium styrene sulfonate-co-maleate)-pV (PSS-CoM-pV) and poly (sodium styrene 4-sulfonate)-pV (PSS-pV). However, no significant change in Ach-mediated responses was observed in the presence of poly (acrylate)-pV (PAA-pV) and DPV-asn. DPV-asn was thus chosen to further elucidate mechanism involved in peroxide mediated modulation of vasoreactivity. DPV-asn (30 nM–300 μM) exerted significantly more stable contractions, that was found to be catalase (100 U/ml) resistant in comparison with H 2 O 2 (30 nM–300 μM) in endothelium intact aortic rings. These contractile responses were found to be dependent on extracellular Ca 2+ and were significantly inhibited in presence of ROS scavenger N-acetylcysteine (100 μM). Intracellular calcium chelation by BAPTA-AM (10 μM) had no significant effect on DPV-asn (30 nM–300 μM) mediated contraction. Pretreatment of aortic rings by rho-kinase inhibitor Y-27632 (10 μM) significantly inhibited DPV-asn-mediated vasoconstriction indicating role of voltage-dependent Ca 2+ influx and downstream activation of rho-kinase. The small initial relaxant effect obtained on addition of DPV-asn (30 nM–1 μM) in PE (1 μM) pre-contracted endothelium intact rings, was prevented in the presence of guanylate cyclase inhibitor, methylene blue (10 μM) and/or nitric oxide synthase (NOS) inhibitor, l -NAME (100 μM) suggesting involvement of nitric oxide and cGMP. DPV-asn, like H 2 O 2 , exerted a response of vasoconstriction in normal arteries and vasodilation at low concentrations (30 nM–1 μM) in PE-pre contracted rings with overlapping mechanisms. These findings suggest usefulness of DPV-asn having low toxicity, in exploring the peroxide-mediated effects on various vascular beds. The present study also convincingly demonstrates role of H 2 O 2 in the modulation of vasoreactivity by using stable peroxide DPV-asn and warrants future studies on peroxide mediated signaling from a newer perspective.
  • References (47)
  • Citations (23)
📖 Papers frequently viewed together
32 Citations
35 Citations
55 Citations
78% of Scinapse members use related papers. After signing in, all features are FREE.
#1Vishal Singh (Central Drug Research Institute)H-Index: 16
#2Manish Jain (Central Drug Research Institute)H-Index: 14
Last. Manoj Kumar Barthwal (Central Drug Research Institute)H-Index: 22
view all 10 authors...
11 CitationsSource
#1Michel B. ToledanoH-Index: 25
Last. Agnès Delaunay-MoisanH-Index: 5
view all 3 authors...
Mammalian cells use hydrogen peroxide (H2O2) not only to kill invading pathogens, but also as a signaling modulator. Woo et al. (2010) now show that the local inactivation of a H2O2-degrading enzyme ensures that the production of this oxidant is restricted to the signaling site.
36 CitationsSource
Rho kinase is involved in the pathogenesis of hypertension, which favors the occurrence of endothelium-dependent contractions. The present study was designed to determine the effects of two Rho kinase inhibitors, HA1077 [1-(5-isoquinolinesulfonyl)-homopiperazine (fasudil)] and Y27632 [(+)-( R )- trans -4-(1-aminoethyl)- N -(4-pyridyl) cyclohexane carboxamide dihydrochloride], on endothelium-dependent and -independent contractions. Isometric tension of 1-year-old spontaneously hypertensive rat an...
28 CitationsSource
#1Wei-Qing Han (SJTU: Shanghai Jiao Tong University)H-Index: 13
#2Dingliang Zhu (SJTU: Shanghai Jiao Tong University)H-Index: 29
Last. Pingjin Gao (SJTU: Shanghai Jiao Tong University)H-Index: 27
view all 6 authors...
Abstract Aims N-acetylcysteine (NAC) has a protective effect against vascular dysfunction by decreasing the level of reactive oxygen species (ROS) in experimental and human hypertension. This study was designed to examine whether NAC would relax vascular rings in vitro via nitric oxide–cyclic guanosine monophosphate (NO–cGMP) pathway, extracellular Ca 2+ and/or K + channels. Main methods Rat aortic arteries were mounted in an organ bath, contracted with 0.1, 0.5 or 1 µmol/L phenylephrine to plat...
11 CitationsSource
#1Maria Regina Freitas (UFPB: Federal University of Paraíba)H-Index: 2
#2Masumi Eto (Thomas Jefferson University)H-Index: 34
Last. Jean-Claude Stoclet (CNRS: Centre national de la recherche scientifique)H-Index: 39
view all 6 authors...
RhoA-activated kinase (ROK) is involved in the disorders of smooth muscle contraction found in hypertension model animals and patients. We examined whether the α1-adrenergic receptor agonist-induced ROK signal is perturbed in resistance small mesentery artery (SMA) of Lyon genetically hypertensive (LH) rats, using a ROK antagonist, Y27632. Smooth muscle strips of SMA and aorta were isolated from LH and Lyon normotensive (LN) rats. After Ca 2+ -depletion and pre-treatment with phenylephrine (PE),...
13 CitationsSource
Protein tyrosine phosphatases (PTPs) are considered to be involved in the etiology of diabetes mellitus, neural diseases such as Alzheimers and Parkinsons disease, regulation of allergy and inflammation, or they are even considered to be responsible for the pathogensvirulence in vivo. Since discovery of first PTP inhibitors such as dephostatin in early 90th years, the research moved on toward search for inhibitors specific for the individual PTP molecules. Currently, dozens of new PTP inhibitors...
84 CitationsSource
#1Diganta Kalita (Tezpur University)H-Index: 14
#2Swapnalee Sarmah (Tezpur University)H-Index: 7
Last. Nashreen S. Islam (Tezpur University)H-Index: 15
view all 7 authors...
32 CitationsSource
#1Marco Giorgio (IEO: European Institute of Oncology)H-Index: 31
#2Mirella TrineiH-Index: 15
Last. Pier Giuseppe Pelicci (IEO: European Institute of Oncology)H-Index: 100
view all 4 authors...
According to the free-radical theory, oxidizing species — including hydrogen peroxide (H2O2) — are generated during aerobic respiration and cause molecular damage and ageing. However, recent evidence suggests that H2O2 that is produced as a signalling molecule by a selected genetic programme regulates ageing.
792 CitationsSource
#1Mohamad Z. Mehdi (UdeM: Université de Montréal)H-Index: 10
#2Zeina M. AzarZ.M. Azar (UdeM: Université de Montréal)H-Index: 3
Last. Ashok K. Srivastava (UdeM: Université de Montréal)H-Index: 25
view all 3 authors...
Excessive generation of reactive oxygen species (ROS) has been implicated in the pathogenesis of many diseases, including atherosclerosis, hypertension, and vascular complications of diabetes. However, the precise mechanisms by which ROS contribute to the development of these diseases are not fully characterized. Hydrogen peroxide (H2O2), a ROS, has been shown to activate several signaling protein kinases, such as extracellular signal-regulated kinase (ERK)1/2 and protein kinase B (PKB) in diffe...
63 CitationsSource
#1Ming-Ho Tsai (NCKU: National Cheng Kung University)H-Index: 2
#2Meei-Jyh Jiang (NCKU: National Cheng Kung University)H-Index: 20
Rho kinase was shown to regulate smooth muscle contraction through modulating myosin phosphatase (MLCP) activity, but the in vivo mechanism remains to be clarified. This study examined the effects of Rho kinase inhibition on the phosphorylation time course of MLCP subunit MYPT1 at Thr697 and Thr855 and MLCP inhibitory protein CPI-17 at Thr38 and on actin polymerization during the contraction of rat tail artery (RTA) smooth muscle. Rho kinase inhibitor Y27632 suppressed force activated by α1-adre...
62 CitationsSource
Cited By23
#1Gangutri Saikia (Tezpur University)H-Index: 3
#2Sandhya Rani Gogoi (Tezpur University)H-Index: 6
Last. Nashreen S. Islam (Tezpur University)H-Index: 15
view all 10 authors...
Calcineurin (CN) is a major calmodulin binding serine/threonine phosphatase which plays a crucial role in numerous mammalian signal transduction pathways. Calcineurin inhibitors represent a valuable tool for elucidating CN dependent cellular processes. The present work deals with the synthesis and comprehensive characterization of a new polymer anchored peroxo niobium complex, Nb-2(O-2)(6)(carboxylate)(2)]-PA (Nb-2) PA=poly(sodium acrylate)], and identification of a set comprising of neat homole...
2 CitationsSource
Abstract Although atherosclerosis is described in New Zealand White rabbit's iliac artery, yet details of time-dependent atherosclerosis progression are not well known. Further, a well characterized accelerated model of atherosclerosis is also required for the screening of candidate drugs to target specific steps of atherosclerosis development. The present study extensively characterizes the time-dependent plaque composition and functional responses of the atherosclerosis in rabbit iliac artery ...
3 CitationsSource
Dexmedetomidine, a highly selective α-2 adrenoceptor agonist, produces vasoconstriction, which leads to transiently increased blood pressure. The goal of this study was to investigate specific protein kinases and the associated cellular signal pathways responsible for the increased calcium sensitization induced by dexmedetomidine in isolated rat aortas, with a particular focus on phosphorylation-dependent inhibitory protein of myosin phosphatase (CPI-17). The effect of Y-27632 and chelerythrine ...
2 CitationsSource
#1Manish JainH-Index: 14
#2Matthieu Zellweger (EPFL: École Polytechnique Fédérale de Lausanne)H-Index: 14
Last. Marie-Noëlle GiraudH-Index: 13
view all 8 authors...
Photodynamic therapy (PDT), which is based on the activation of photosensitizers with light, can be used to reduce plaque burden. We hypothesized that intra-arterial photosensitizer administration and photo-activation will lead to high and rapid accumulation within the plaque with reduced systemic adverse effects. Thus this “intra-arterial” PDT would be expected to have less side effects and due to the short time involved would be compatible with percutaneous coronary interventions. Aim: We char...
7 CitationsSource
#1Nirupama Chatterjee (Centre for DNA Fingerprinting and Diagnostics)H-Index: 3
#2Tarique Anwar (Centre for DNA Fingerprinting and Diagnostics)H-Index: 1
Last. Gayatri Ramakrishna (Centre for DNA Fingerprinting and Diagnostics)H-Index: 18
view all 5 authors...
Hydrogen peroxide is often required in sublethal, millimolar concentrations to show its oxidant effects on cells in culture as it is easily destroyed by cellular catalase. Previously, we had shown that diperoxovanadate, a physiologically stable peroxovanadium compound, can substitute H2O2 effectively in peroxidation reactions. We report here that peroxovanadate when anchored to polyacrylic acid (PAPV) becomes a highly potent inhibitor of growth of lung carcinoma cells (A549). The early events as...
2 CitationsSource
#1Yean Chun LohH-Index: 5
#2Chu Shan TanH-Index: 5
Last. Mun Fei YamH-Index: 20
view all 6 authors...
This paper is a review on the types of antagonists and the signaling mechanism pathways that have been used to determine the mechanisms of action employed for vasodilation by test compounds. Thus, we exhaustively reviewed and analyzed reports related to this topic published in PubMed between the years of 2010 till 2015. The aim of this paperis to suggest the most appropriate type of antagonists that correspond to receptors that would be involved during the mechanistic studies, as well as the lat...
10 CitationsSource
#1Maryam Rameshrad (Tabriz University of Medical Sciences)H-Index: 12
#2Hossein Babaei (Tabriz University of Medical Sciences)H-Index: 13
Last. Daniel F. Fouladi (Tabriz University of Medical Sciences)H-Index: 7
view all 4 authors...
Abstract Rat aorta assay provides a low cost and rapid platform, especially for preclinical in vivo models. The signaling pathways of the analog on the vessels could be evaluated separately on the endothelium or smooth muscle cells by rings of the rat aorta in vitro. The rat aorta is used for angiogenesis modeling to integrate the benefits of the both in vivo and in vitro models. These explain the importance and usage of rat aorta in researches. Furthermore, about 4503 articles have been publish...
17 CitationsSource
#1Nashreen S. Islam (Tezpur University)H-Index: 15
#2Jeena Jyoti Boruah (Tezpur University)H-Index: 9
Our recent achievements concerning the synthesis and characterization of water soluble peroxo complexes of V(V) and Mo(VI) in macroligand environment, as well as some key features of biological relevance of these compounds, such as their hydrolytic stability, activity with phosphohydrolase enzyme vis-a-vis free peroxovanadium (pV) or peroxomolybdenum (pMo) complexes, and their activity in biomimetic oxidative bromination are presented here. Immobilization of pMo species on insoluble polymer matr...
8 CitationsSource
#1Vishal Singh (Central Drug Research Institute)H-Index: 16
#2Manish Jain (Central Drug Research Institute)H-Index: 14
Last. Manoj Kumar Barthwal (Central Drug Research Institute)H-Index: 22
view all 9 authors...
Background & objectives: Curcuma oil (C. oil) isolated from turmeric (Curcuma longa L.) has been shown to have neuro-protective, anti-cancer, antioxidant and anti-hyperlipidaemic effects in experimental animal models. However, its effect in insulin resistant animals remains unclear. The present study was carried out to investigate the disease modifying potential and underlying mechanisms of the C. oil in animal models of diet induced insulin resistance and associated thrombotic complications. Me...
6 CitationsSource
#1Gurpreet Kaur (Integral University)H-Index: 4
#2Neetu SinghH-Index: 24
Last. Kashif Hanif (AcSIR: Academy of Scientific and Innovative Research)H-Index: 1
view all 9 authors...
AbstractContext: Withania somnifera (Linn.) Dunal (Solanaceae), a clinically used herbal drug in Ayurveda, shows potent antioxidant, anti-inflammatory, pro-apoptotic, and cardioprotective effects. However, the efficacy of W. somnifera in pulmonary hypertension (PH), a cardiopulmonary disorder, remains unexplored.Objective: The present study investigates the effect of W. somnifera root powder on monocrotaline (MCT)-induced PH in rats.Materials and methods: In preventive studies, W. somnifera root...
7 CitationsSource