Role of Angiotensin II and Free Radicals in Blood Pressure Regulation in a Rat Model of Renal Hypertension

Dobrian, Anca D.; Schriver, Suzanne D.; Prewitt, Russell L.

doi:10.1161/01.hyp.38.3.361

Cited by 88 publications

(69 citation statements)

References 63 publications

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“…In these studies, arteries distal of the stenosis had low vascular O 2 Ϫ production, whereas O 2 Ϫ production was increased in the vascular areas exposed to hypertension and this is associated with the induction of NADPH oxidase subunits and protein kinase C. 29 -31 Also endothelial NO formation is increased in response to enhanced circumferential tension, 32 and peroxynitrite formation has uniformly been observed in models of high-volume hypertension. 22,28 The data obtained with eNOS Ϫ/Ϫ mice in this study suggest a critical role of endothelial NO for the action of recombinant ecSOD. eNOS-derived ONOO Ϫ could potentially inactivate abundantly expressed endogenous ecSOD, rendering the system sensitive to the exogenously applied enzyme.…”

Section: Discussionmentioning

confidence: 73%

“…14 At that stage, which is usually reached after 2 weeks, blockade of the AT1 receptor does not affect blood pressure in rats 21 or 8-isoprostane level. 22 The effects of high-volume hypertension on the vascular radical formation have not been extensively studied, and despite the observation that antioxidants lower the blood pressure in the 1K1C model, the enzymatic sources of ROS are currently unknown. 22 Although the 1K1C model has similarities to the DOCA and salt model of high-volume hypertension, sodium retention is achieved via a mineralocorticoid-independent mechanism in the 1K1C model.…”

Section: Discussionmentioning

confidence: 99%

“…22 The effects of high-volume hypertension on the vascular radical formation have not been extensively studied, and despite the observation that antioxidants lower the blood pressure in the 1K1C model, the enzymatic sources of ROS are currently unknown. 22 Although the 1K1C model has similarities to the DOCA and salt model of high-volume hypertension, sodium retention is achieved via a mineralocorticoid-independent mechanism in the 1K1C model. This aspect might be important as mineralocorticoids activate the NADPH oxidase 23 and as the mineralocorticoid antagonist spironolactone lowers vascular superoxide anion formation in some disease models.…”

Section: Discussionmentioning

confidence: 99%

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Inactivation of Extracellular Superoxide Dismutase Contributes to the Development of High-Volume Hypertension

Jung

Marklund

Xia

et al. 2007

ATVB

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Objectives-Extracellular superoxide dismutase (ecSOD) lowers superoxide anions and maintains vascular nitric oxide level. We studied the function of ecSOD in high-volume hypertension induced by the 1-kidney-1-clip model in wild-type, ecSOD Ϫ/Ϫ mice, and endothelial nitric oxide synthase (eNOS) Ϫ/Ϫ mice. Methods and Results-The 1-kidney-1-clip model resulted in impaired endothelium-dependent relaxation and hypertension and vascular oxidative stress in wild-type and ecSOD Ϫ/Ϫ mice. Recombinant ecSOD lowered the blood pressure and improved aortic nitric oxide bioavailability in wild-type and ecSOD Ϫ/Ϫ but not eNOS Ϫ/Ϫ mice. ecSOD had no effect on blood pressure in eNOS Ϫ/Ϫ or wild-type mice treated with a nitric oxide synthase inhibitor. The 1-kidney-1-clip model markedly induced ecSOD protein expression, whereas activity was increased by only 25%, suggesting a partial inactivation of ecSOD in high-volume hypertension. Incubation of aortic segments with peroxynitrite or hydrogen peroxide attenuated ecSOD activity, but peroxynitrite did not induce tyrosine nitration of ecSOD, suggesting oxidative inactivation of the enzyme. Administration of polyethyleneglycol-catalase for 3 days selectively lowered the blood pressure in ecSOD ϩ/ϩ but not ecSOD Ϫ/Ϫ mice and improved nitric oxide bioavailability. In contrast, acute application of catalase had no effect. Conclusions-Nitric

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Section: Discussionmentioning

confidence: 73%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Inactivation of Extracellular Superoxide Dismutase Contributes to the Development of High-Volume Hypertension

Jung

Marklund

Xia

et al. 2007

ATVB

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“…It catalyzes the conversion of O 2 · Ϫ radicals to hydroperoxides (30,31). Tempol has been used to investigate the role of O 2 · Ϫ radicals in several pathophysiologic conditions, such as ischemia-reperfusion (40,41), radiation (42,43), diabetes mellitus (44), and hypertension (32,45,46). Tempol significantly reduced the effect of sub-pressor dose of AngII on the renal excretion of 8-iso PGF 2␣ .…”

Section: Discussionmentioning

confidence: 99%

A Mouse Model of Angiotensin II Slow Pressor Response

Kawada

Imai

Karber³

et al. 2002

Journal of the American Society of Nephrology

181

183

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Abstract. The slow pressor response to prolonged infusions of angiotensin II (AngII) entails a delayed rise in BP. This study investigated the hypothesis that the response depends on the generation of oxidative stress. The BP and renal functional response of mice to graded doses (200, 400, and 1000 ng · kg Ϫ1 · min Ϫ1 ) of subcutaneously infused AngII was studied. The SBP of conscious mice increased by day 3 at AngII1000 but showed a delayed rise by days 9 to 13 (slow pressor response) at the lower rates of AngII infusion. By day 13, there was a graded increase in SBP with the rate of AngII infusion (Vehicle, Ϫ2.6 Ϯ 2.6%; AngII200, ϩ14.1 Ϯ 5.0%; AngII400, ϩ31.9 Ϯ 1.9%; AngII1000, ϩ43.2 Ϯ 5.5%). The MAP measured under anesthesia rose significantly (P Ͻ 0.001) with AngII400 at 14 d (Vehicle, 85 Ϯ 2 mmHg; AngII400, 100 Ϯ 3 mmHg). When studied at day 6, the MAP of AngII400 rats was not elevated (88 Ϯ 2 mmHg; NS versus vehicle), yet the GFR was higher (1.05 Ϯ 0.05 versus 1.25 Ϯ 0.05 ml · min Ϫ1 · g Ϫ1 ; P Ͻ 0.05) accompanied by an increase in the filtration fraction (FF) (28.8 Ϯ 1.2 versus 37.2 Ϯ 0.8%; P Ͻ 0.001). From day 6 through day 14, the MAP had increased (P Ͻ 0.01) in AngII400, accompanied by a significant reduction in GFR to 1.05 Ϯ 0.04 ml · min Ϫ1 · g Ϫ1 (P Ͻ 0.01) and elevation of renal vascular resistance (RVR) (day 6 versus day 14, 15.3 Ϯ 0.6 versus 19.2 Ϯ 1.2 mmHg · ml Ϫ1 · min Ϫ1 · g Ϫ1 ; P Ͻ 0.05). Renal excretion of 8-iso PGF 2␣ was increased in AngII400 group at day 12 (2.52 Ϯ 0.35 versus 5.85 Ϯ 0.78 pg · day Ϫ1 ; P Ͻ 0.01). The permeant superoxide dismutase mimetic tempol reduced the effects of AngII400 on the SBP (Ϫ1.7 Ϯ 5.8%; P Ͻ 0.01), the MAP (87 Ϯ 4 mmHg; P Ͻ 0.01), and the RVR (15.2 Ϯ 0.5 mmHg · ml Ϫ1 · min Ϫ1 · g Ϫ1 ; P Ͻ 0.05) at day 14 and the renal 8-iso PGF 2␣ excretion (3.53 Ϯ 0.71 pg · d Ϫ1 ; P Ͻ 0.05) at day 12. It is concluded that the AngII infused mouse is a valid model for the slow pressor response. There is an early rise in GFR and FF, consistent with increased postglomerular vascular resistance and a late rise in RVR with a fall in GFR, consistent with increased preglomerular vascular resistance that is accompanied by a rise in BP. There is evidence of increased oxidative stress that is implicated in the increase in the BP and RVR in this model.The angiotensin II (AngII) slow pressor response is a gradually developing increase in BP (BP) with an initially subpressor rate of infusion (1-4). The slow pressor response was first described in rats in 1963, (1) and subsequently has been demonstrated in rabbits, dogs and man (5). Whereas the plasma AngII levels increase by about 80-fold during an immediate pressor response, they are elevated within a physiologic level of 2-to sixfold during a slow pressor response (6). A slow pressor response is seen also with the thromboxane A2/prostaglandin H2 (TP) receptor mimetic, U-46619 (7,8). This slow pressor response has been considered an excellent model for renal hypertension in which both AngII type I (AT1) and TP receptor have been implica...

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“…66 Renovascular hypertension (RVH), an Ang II-dependent form of hypertension, is accompanied by increased oxidative stress in animal models 67 and human subjects. 68 The cell-permeable SOD mimetic tempol lowers blood pressure in the 1-kidney, 1-clip model of RVH 69 Oxidative stress plays a role in low renin hypertension as well. In the DOCA-salt hypertension model, vascular production of O 2 ·Ϫ is increased in association with upregulation of p22phox, 70 and long-term treatment with tempol lowers blood pressure.…”

Section: Hypertensionmentioning

confidence: 99%

Molecular and Cellular Mechanisms

2010

Radiation Hormesis and the Linear-No-Threshold Assumption

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Abstract-Accumulating evidence indicates that reactive oxygen species (ROS) play major roles in the initiation and progression of cardiovascular dysfunction associated with diseases such as hyperlipidemia, diabetes mellitus, hypertension, ischemic heart disease, and chronic heart failure. ROS produced by migrating inflammatory cells as well as vascular cells (endothelial cells, vascular smooth muscle cells, and adventitial fibroblasts) have distinct functional effects on each cell type. These include cell growth, apoptosis, migration, inflammatory gene expression, and matrix regulation. ROS, by regulating vascular cell function, can play a central role in normal vascular physiology, and can contribute substantially to the development of vascular disease. Key Words: antioxidants Ⅲ vascular disease Ⅲ muscle, smooth, vascular Ⅲ endothelium Ⅲ free radicals Ⅲ macrophages Ⅲ oxidative stress A ccumulating evidence indicates that oxidative stress plays a major role in the initiation and progression of cardiovascular dysfunction associated with diseases such as hyperlipidemia, diabetes mellitus, hypertension, ischemic heart disease, and chronic heart failure. Oxidative stress is a state in which excess reactive oxygen species (ROS) overwhelm endogenous antioxidant systems. ROS have distinct functional effects on each cell type in the vasculature and can play both physiological and pathophysiological roles. In this review, we will focus on vascular endothelial cells (ECs) and smooth muscle cells (VSMCs), because the effects of ROS on adventitial fibroblasts were reviewed recently. 1 We will also briefly discuss the clinical implications of oxidative stress. Reactive Oxygen Species Enzymatic Superoxide ProductionMultiple enzymatic systems produce O 2 ·Ϫ and its derivatives in the vasculature, including NAD(P)H oxidases, XO, nitric oxide synthases (NOS), and MPO. The relative importance of each of these proteins appears to vary with the physiological state of the vasculature. NAD(P)H oxidases consist of multiple subunits: the electron transfer moieties (gp91phox, nox1 or nox4), p22phox, and regulatory subunits (p47phox, p67phox, and rac1). The expression pattern of these subunits varies among vascular cells. 4 What makes the NAD(P)H oxidases so important in vascular function is their responsiveness to a variety of agonists, such as angiotensin (Ang) II. 5 Enzyme activation occurs over the short term by stimulation of specific intracellular signals 6 and over the long term by upregulation of the enzyme subunits. 7,8 Even low Ang II concentrations (0.1 nmol/L) increase NAD(P)H oxidase-derived ROS, suggesting that this enzyme system is important physiologically. 5 In ROS have been implicated in various clinicopathologic entities, including ischemia/reperfusion injury, hypercholesterolemia and endothelial dysfunction in chronic heart failure. 11,12 Recently, the role of MPO in vascular pathology has been highlighted. MPO is abundant in phagocytes and catalyzes H 2 O 2 to produce HOCl and other oxidizing species. 13 It also uti...

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Role of Angiotensin II and Free Radicals in Blood Pressure Regulation in a Rat Model of Renal Hypertension

Cited by 88 publications

References 63 publications

Inactivation of Extracellular Superoxide Dismutase Contributes to the Development of High-Volume Hypertension

Inactivation of Extracellular Superoxide Dismutase Contributes to the Development of High-Volume Hypertension

A Mouse Model of Angiotensin II Slow Pressor Response

Molecular and Cellular Mechanisms

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