Increased vascular endothelin-1 gene expression with unaltered nitric oxide synthase levels in fructose-induced hypertensive rats

Lee, Dong Hoon; Lee, Jong-Un; Kang, Dae Gill; Paek, Yun Woong; Chung, Dong Jin; Chung, Min Young

doi:10.1053/meta.2001.19527

Cited by 28 publications

(19 citation statements)

References 32 publications

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“…29 However, Liu et al 23 demonstrated that the vascular NO pathway may not be causally related to the development of fructose-induced hypertension. 28 In a previous study, we showed that angiotensin II induces superoxide generation, which impairs NO production in the NTS. 10 The depressor effect of NO in the NTS occurs through the inhibition of sympathetic nervous activity.…”

Section: Discussionmentioning

confidence: 92%

“…27 Furthermore, in a clinical setting, derangements of the peripheral endothelial NO system have been related to the development of hypertension. 28 It may be a pathogenic factor for abnormal regulation of vascular tones through imbalance of NO and superoxide production, which may be associated with the development of hypertension in the insulin-resistant state. 29 However, Liu et al 23 demonstrated that the vascular NO pathway may not be causally related to the development of fructose-induced hypertension.…”

Section: Discussionmentioning

confidence: 99%

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Caffeine Intake Improves Fructose-Induced Hypertension and Insulin Resistance by Enhancing Central Insulin Signaling

et al. 2014

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535I n humans, the intake of sugar-sweetened beverages is correlated with the prevalence of type 2 diabetes mellitus and obesity.1 High fructose intake is used as a well-established animal model for insulin resistance.2 Some studies have shown that chronic fructose intake in normal rats induces hypertension in association with insulin resistance.2,3 However, insulin infusion was found to stimulate local vasodilation by enhancing the action of nitric oxide (NO). 4 The effect of insulin on the baroreceptor reflex in nucleus tractus solitarii (NTS) is probably mediated by a change in sympathetic nervous activity. 4,5 Furthermore, sympathectomy can prevent the development of fructose-induced hypertension in rats. 6 Recent studies suggest that fructose consumption increases superoxide generation and attenuates baroreflex response. 7,8 Interestingly, inhibition of superoxide generation in NTS can reduce blood pressure (BP) in stroke-prone hypertensive rats. 9 The NTS is located in the dorsal medulla of the brain stem, which is the primary integrating center for cardiovascular regulation and other autonomic functions of the central nervous system. Furthermore, NO has important modulatory functions in the NTS, including the modulation of arterial BP and sympathetic nerve activity. 10 In previous experiments, we demonstrated that insulin microinjected into the NTS induces a depressor effect and initiates an interaction between insulin and phosphatidylinositol 3-kinase Abstract-Recent clinical studies found that fructose intake leads to insulin resistance and hypertension. Fructose consumption promotes protein fructosylation and formation of superoxide. In a previous study, we revealed that inhibition of superoxide production in the nucleus tractus solitarii (NTS) reduces blood pressure. Caffeine displays significant antioxidant ability in protecting membranes against oxidative damage and can lower the risk of insulin resistance. However, the mechanism through which caffeine improves fructose-induced insulin resistance is unclear. The aim of this study was to investigate whether caffeine consumption can abolish superoxide generation to enhance insulin signaling in the NTS, thereby reducing blood pressure in rats with fructose-induced hypertension. Treatment with caffeine for 4 weeks decreased blood pressure, serum fasting glucose, insulin, homeostatic model assessment-insulin resistance, and triglyceride levels and increased the serum direct high-density lipoprotein level in fructose-fed rats but not in control rats. Caffeine treatment resulted in the recovery of fructose-induced decrease in nitric oxide production in the NTS. Immunoblotting and immunofluorescence analyses further showed that caffeine reduced the fructoseinduced phosphorylation of insulin receptor substrate 1 (IRS1 S307) and reversed Akt S473 and neuronal nitric oxide synthase phosphorylation. Similarly, caffeine was able to improve insulin sensitivity and decrease insulin levels in the NTS evoked by fructose. Caffeine intake also reduced the production o...

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Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Caffeine Intake Improves Fructose-Induced Hypertension and Insulin Resistance by Enhancing Central Insulin Signaling

et al. 2014

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“…9,24) ET-1 is also thought to be an important vasoactive peptide contributing to the development of hypertension in this experimental model. 9,25) ET-1 is mostly produced in endothelial cells (EC) and acts on various tissues in an endocrine, paracrine, or autocrine manner as a strong endogenous vasoconstrictor and as a growth factor for vascular smooth muscle cells. 26,27) Thus, ET-1 may promote vascular hypertrophy and atherosclerosis.…”

Section: Discussionmentioning

confidence: 99%

Effects of Morin on Blood Pressure and Metabolic Changes in Fructose-Induced Hypertensive Rats

Kang

Moon

Sohn

et al. 2004

Biological & Pharmaceutical Bulletin

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Insulin resistance has long been recognized to be associated with hypertension, hyperinsulinemia and dyslipidemia. 1,2) These are also critical components of recently re-defined metabolic syndrome. [3][4][5] Insulin resistance and hyperinsulinemia have been demonstrated in not only genetic, but also nongenetic rat models of hypertension, such as the spontaneously hypertensive, 6) Dahl salt-sensitive, 7) Milan hypertensive, 8) and fructose-fed rat, 1,9) suggesting that mechanism leading to hypertension may be shared by these experimental models. Fructose-induced hypertension in rats represents an acquired model of insulin resistance such as metabolic syndrome (also known as syndrome X).10) Chronic fructose treatment in rats has been shown to elevate blood pressure in association with insulin resistance, hyperinsulinemia, and hypertriglyceridemia. Although the mechanisms underlying fructose-induced hypertension are not completely established, it has been proposed that increase in blood pressure in fructose-fed rats is secondary to the development of insulin resistance and hyperinsulinemia. 1,9) The flavonoids are a large group of plant-derived compounds that are known to exhibit a lot of biological effects including reducing plasma levels of low density lipoprotein, 11) scavenging reactive oxygen species, 12) inhibiting platelet aggregation, 13,14) and inhibiting carcinogenesis. 15) In addition, a number of flavonoids have been reported to dilate vascular smooth muscle and then reduce blood pressure in various animal models of hypertension. [16][17][18] Morin (3,5,7,2Ј,4Ј-pentahydroxyflavone; Fig. 1) is a kind of flavonoid found in the fig and other Moraceae, which are used as herbal medicines. 19,20) A very wide range of biological actions of morin including antioxidant properties, 21) inhibitory activity of oxidative modification of low density lipoprotein, 11) and vasorelaxant effect 22) has been reported. Such beneficial effects of morin could be expected to work in human or animal models of various diseases including metabolic syndrome, cardiovascular disease, and diabetes. However, there is little information about in vivo effects of morin in animal models or patients with above diseases. Therefore, in the present study, we examined the effects of chronic administration of morin on the blood pressure, renal function, and lipid metabolites in rats with HF-induced hypertension. MATERIALS AND METHODS Experimental DesignThe animal procedures were in strict accordance with the National Institutes of Healthy Guidelines for the Care and Use of laboratory Animals and were approved by the Institutional Animal Care and Utilization Committee. Male Sprague-Dawley rats (200-220 g) were purchased from Korean Experimental Animals Co. (Daejeon, Korea). The rats were housed in metabolic cages to collect 24-h urine samples in the animal room with an automatic temperature (22°C) and lighting (12 h light-dark cycle) control. An adaptation period of 1 week for vehicle (tap water) administration and blood pressure measurements wa...

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“…46 In the present study, the expression of aortic eNOS protein was not significantly different between the control rats and FFR, and this finding is consistent with other reports. 4,24 It is speculated that there may be different underlying mechanisms to enhance the production of eNOS in the aorta and kidney. Because the systolic blood pressure of FFR was slightly higher than that of control rats, even on a low-sodium diet, the hypertension seen in FFR was thought to be not only salt sensitive but also salt insensitive.…”

Section: Discussionmentioning

confidence: 99%

Decrease in Renal Medullary Endothelial Nitric Oxide Synthase of Fructose-Fed, Salt-Sensitive Hypertensive Rats

et al. 2002

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Abstract-We investigated the expression of endothelial NO synthase (eNOS) in the kidneys of fructose-fed insulin-resistant rats (FFR) with a low-or high-sodium diet. Male Sprague-Dawley rats were fed a control (C) or high-fructose (40% fructose; F) diet, with each coming in low-sodium (0.024% NaCl; LS-C or LS-F) or high-sodium (3% NaCl; HS-C or HS-F) varieties, for 2 weeks. Half of the FFR were orally administered pioglitazone (10 mg ⅐ kg Ϫ1 ⅐ day Ϫ1 ), an insulin-sensitizing agent (LS-FP or HS-FP). The systolic blood pressure was significantly higher in the HS-F rats than in the LS-F rats or the HS-C rats (HS-F rats, 129Ϯ4 mm Hg, versus LS-F rats, 115Ϯ3 mm Hg, PϽ0.05; or versus HS-C rats, 116Ϯ5 mm Hg, PϽ0.05), which indicated the salt dependence of hypertension in FFR. The protein expression of eNOS in the renal medulla of FFR was significantly lower than that in control rats during a high sodium load. The administration of pioglitazone prevented the hypertension (HS-F rats, 129Ϯ4 mm Hg, versus HS-FP rats, 113Ϯ3 mm Hg, PϽ0.05) and the reduction of medullary eNOS protein expression in HS-F rats. There was no significant difference in eNOS expression in the renal cortex or aorta between FFR and control rats, regardless of sodium load. These results suggest that the decrease in renal medullary NO production by eNOS during a high sodium load may play a role in fructose-fed, salt-sensitive hypertension. Key Words: insulin resistance Ⅲ fructose Ⅲ hypertension, sodium-dependent Ⅲ nitric oxide synthase Ⅲ kidney P revious studies have shown an association between insulin resistance and systemic hypertension. 1,2 Compensatory hyperinsulinemia was thought to cause hypertension because it led to sodium retention, sympathetic nerve activation, and vascular smooth muscle cell proliferation. 2 However, Bursztyn et al 3 demonstrated that chronic exogenous hyperinsulinemia itself did not elevate blood pressure; only when in combination with a defective NO system, might hyperinsulinemia cause hypertension. Some investigators revealed a correlation between insulin resistance and defects of the NO system, 4,5 and others have shown that a defective NO system in the kidney 6 or the whole body 7 could be the cause of hypertension.Renal NO is an important controller of urinary sodium excretion, 8 so a defect of the NO system in the kidney can become the cause of salt-sensitive hypertension. 6,9,10 If the defect of the NO system is seen in the kidney of insulin-resistant subjects, they may develop salt-sensitive hypertension. Indeed, several investigators indicate that patients 11,12 or animals 13,14 with insulin resistance tend to develop saltsensitive hypertension. Although the mechanisms underlying the coexistence of insulin resistance and hypertension remain unclear, a defect of the NO system in the kidney is thought to be a cause of hypertension in insulin-resistant subjects. 13 NO is produced from the conversion of L-arginine to L-citrulline by a family of enzymes known as NO synthase (NOS). 15 NOS exists in 3 isoforms: neuronal ...

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Increased vascular endothelin-1 gene expression with unaltered nitric oxide synthase levels in fructose-induced hypertensive rats

Cited by 28 publications

References 32 publications

Caffeine Intake Improves Fructose-Induced Hypertension and Insulin Resistance by Enhancing Central Insulin Signaling

Caffeine Intake Improves Fructose-Induced Hypertension and Insulin Resistance by Enhancing Central Insulin Signaling

Effects of Morin on Blood Pressure and Metabolic Changes in Fructose-Induced Hypertensive Rats

Decrease in Renal Medullary Endothelial Nitric Oxide Synthase of Fructose-Fed, Salt-Sensitive Hypertensive Rats

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