Intracellular Na+ and Ca2+ in aortic smooth muscle cells after enzymatic isolation in spontaneously hypertensive rats

Zidek, Walter; Kerényi, T; Losse, H; Vetter, Hans

doi:10.1007/bf01851778

Cited by 20 publications

(9 citation statements)

References 14 publications

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“…21 Briefly, the intima and adventitia were dissected, and the media was digested with 0.1% collagenase, 0.05% elastase, 0.375 mg/mL trypsin inhibitor from soybean, and 2 mg/mL albumin fraction V. The cells were cultured in DMEM with FCS (10% [vol/vol]), penicillin (100 U/mL)/streptomycin (100 g/mL), and 2 mmol/L L-glutamine. The cells reacted with a smooth muscle ␣-actin antibody that selectively recognizes SMCs but does not react with endothelial cells or fibroblasts.…”

Section: Cell Preparation and Culturementioning

confidence: 99%

Endothelin-1 and Smooth Muscle Cells

Fei¹,

Viedt²,

Soto³

et al. 2000

ATVB

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Abstract-Endothelin-1 (ET-1) has been proposed to contribute to atherogenesis and plaque rupture in coronary heart disease through activation of mitogen-activated protein kinases (MAPKs) in smooth muscle cells (SMCs). Reactive oxygen species (ROS) have been shown to be important signal transduction molecules in SMCs. Thus, the present study aimed to assess the role of ROS in ET-1-mediated activation of c-Jun amino-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) 1/2. Rat SMCs were exposed to ET-1 over time at concentrations from 10 Ϫ6 to 10 Ϫ10 mol/L, and MAPK activity was quantified. Activation of JNK and ERK was observed with a maximum stimulation at 10 Ϫ7 mol/L ET-1. JNK and ERK were activated by ET-1 binding to a single receptor (ET-1A) but differed in their downstream mechanisms: only JNK activation was sensitive to the radical scavenger N-acetylcysteine and diphenylene iodonium, an inhibitor of NADPH oxidase, indicating a role for ROS. The downstream MAPK effector and proinflammatory transcription factor, the activator protein-1 complex, was maximally activated 2 hours after the addition of ET-1. It was mainly composed of the JNK substrate c-Jun, and activation was also dependent on ROS formation. We suggest that plaque activation by ET-1 can be mediated through ROS. It can be hypothesized that the clinical benefit of antioxidants in the treatment of atherogenesis may partially depend on neutralization of ET-1-mediated ROS production. Key Words: endothelin-1 Ⅲ atherosclerosis Ⅲ reactive oxygen species Ⅲ mitogen-activated protein kinase Ⅲ smooth muscle S everal lines of evidence suggest a role for endothelin-1 (ET-1) in the pathogenesis of atherosclerosis, including immunohistochemical studies demonstrating an increased accumulation of ET-1 in human atheroma. 1 Furthermore, a direct correlation could be shown between the amount of ET-1 present in human coronary artery lesions and unstable angina. 2 In animal experiments, endothelin antagonists had a protective effect against atherosclerosis. 3,4 A release of endothelin, in vitro, by smooth muscle cells (SMCs) themselves was also demonstrated. 5 The proatherogenic properties of endothelin are attributed to its vasoconstrictive action, 2,6,7 and more recently, ET-1 has been reported to activate SMCs. 8,9 As shown by numerous studies, activation of SMCs can be an important step in the inflammatory response of the vessel wall. 10 The inflammatory response of SMCs involves a number of proteins of the signal cascade, including the inducible transcription factors c-Jun and c-Fos. 11 These are expressed at very low levels in quiescent SMCs but can be induced by stimulating SMCs with different agents, such as angiotensin II 12 or platelet-derived growth factor. 13 When activated, c-Jun and c-Fos can dimerize to form activator protein-1 (AP-1), a transcription factor complex. 14 Expression and activation of AP-1 proteins is tightly controlled by mitogen-activated protein (MAP) kinases, such as the c-Jun amino-terminal kinase (JNK) and extracellul...

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Section: Cell Preparation and Culturementioning

confidence: 99%

Endothelin-1 and Smooth Muscle Cells

Fei¹,

Viedt²,

Soto³

et al. 2000

ATVB

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“…but also of vascular smooth muscle cell (VSMC) growth (see References 1 and 2 for reviews). In hypertension, both the functional and structural integrity of vascular smooth muscle are deranged, 12 thus invoking an essential involvement of Ang II in the pathophysiology of hypertension. This is supported by observations that angiotensin converting enzyme inhibitors effectively lower blood pressure 3 and also prevent myointimal proliferation after vascular injury.…”

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confidence: 99%

“…First, decreased Ca 2+ binding by the inner surface of plasma membrane and increased intracellular free calcium concentration ([Ca 2+ ]i) have been demonstrated in erythrocytes 8 - 9 and platelets 1011 from spontaneously hypertensive rats (SHRs) and patients with essential hypertension. Second, increased [Ca 2+ ]; concentrations have been demonstrated in lysed VSMCs using Ca 2+ -selective electrodes 12 and in intact VSMCs using fluorescent Ca 2+ -indicator techniques. 13 Third, an increased sensitivity to several vasoconstrictors as well as extracellular Ca 2+ concentration occurs in vascular beds of SHRs at the prehypertensive stage.…”

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confidence: 99%

Vascular smooth muscle cell calcium fluxes. Regulation by angiotensin II and lipoproteins.

et al. 1993

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This study examined 4SCa uptake, 45 Ca efflux, and the distribution of exchangeable 4SCa in confluent, quiescent cultures of aortic smooth muscle cells (VSMCs) from normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs). These parameters were investigated under basal conditions and after addition of angiotensin II (Ang II) and low (LDL) (Ang II) 1 is an important regulator / \ not only of vascular smooth muscle contraction A. A . but also of vascular smooth muscle cell (VSMC) growth (see References 1 and 2 for reviews). In hypertension, both the functional and structural integrity of vascular smooth muscle are deranged, 12 thus invoking an essential involvement of Ang II in the pathophysiology of hypertension. This is supported by observations that angiotensin converting enzyme inhibitors effectively lower blood pressure 3 and also prevent myointimal proliferation after vascular injury. 4 Hypertension greatly increases the frequency of atherosclerotic cardiovascular sequelae, and lipoproteins greatly affect the impact of hypertension on the pace of atherogenesis (see References 5 and 6 for reviews). The two diseases are closely linked with respect to predisposing risk factors, clinical manifestations, and vascular/cellular pathobiology; thus, the fundamental role of lipoproteins in the atherosclerotic process suggests that they may also be involved in the pathophysiology of hyper- tension. 5-6 Evidence is accumulating to indicate that low density lipoprotein (LDL) and high density lipoprotein (HDL) can influence smooth muscle cell processes that are distinct from those related to cholesterol homeostasis per se, such as growth-related metabolic events, cell morphology, and proliferation and contractile processes (reviewed in Reference 7).Calcium is a pivotal signaling molecule in the regulation of smooth muscle structure and function, and the hypothesis on the involvement of abnormalities of intracellular calcium handling in the pathophysiology of hypertension is based on the following principal observations.

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“…The elevation of the intracellu lar calcium seems to reflect a generalized metabolic alter ation. since it was found in various tissues as vascular smooth muscle cells [3], red cells [2], and platelets [1].…”

Section: Introductionmentioning

confidence: 99%

“…In creased intracellular free calcium concentrations were found in essential hypertension [1. 2] and in sponta neously hypertensive rats [3], Since calcium plays a major role in muscular contraction, its elevation in vascular smooth muscle cells is supposed to enhance the vessel tone in hypertension [4]. The elevation of the intracellu lar calcium seems to reflect a generalized metabolic alter ation.…”

Section: Introductionmentioning

confidence: 99%