Renin–angiotensin system and fibronectin gene expression in Dahl Iwai salt-sensitive and salt-resistant rats

Tamura, Kouichi; Chiba, Eiko; Yokoyama, Nobuyuki; Sumida, Yoichi; Yabana, Machiko; Tamura, Nobuko; Takasaki, Izumi; Takagi, Nobuyoshi; Ishii, Masao; Horiuchi, Masatsugu; Umemura, Satoshi

doi:10.1097/00004872-199917010-00013

Cited by 31 publications

(25 citation statements)

References 39 publications

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“…However, Dahl-S rats fed a normal diet demonstrated lower plasma and tissue angiotensin II than Dahl-R rats, but salt loading did not cause significant changes in angiotensin II levels in either strain. 31,32 Thus, it is unlikely that angiotensin II is involved in the pathogenesis of insulin resistance in the Dahl-S rat on a high-salt diet.…”

Section: Discussionmentioning

confidence: 99%

High-Salt Diet Enhances Insulin Signaling and Induces Insulin Resistance in Dahl Salt-Sensitive Rats

et al. 2002

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Abstract-A high-salt diet, which is known to contribute to the pathogenesis of hypertension, is also reportedly associated with insulin resistance. We investigated the effects of a high-salt diet on insulin sensitivity and insulin signaling in salt-sensitive (Dahl-S) and salt resistant (Dahl-R) strains of the Dahl rat. Evaluation of hyperinsulinemic-euglycemic clamp studies and glucose uptake into the isolated soleus muscle revealed that salt loading (8% NaCl) for 4 weeks induced hypertension and significant insulin resistance in Dahl-S rats, whereas no significant effects were observed in Dahl-R rats. Despite the presence of insulin resistance, insulin-induced tyrosine phosphorylation of the insulin receptor and insulin receptor substrates, activation of phosphatidylinositol 3-kinase, and phosphorylation of Akt were all enhanced in Dahl-S rats fed a high-salt diet. The mechanism underlying this form of insulin resistance thus differs from that previously associated with obesity and dexamethasone and is likely due to the impairment of one or more metabolic steps situated downstream of phosphatidylinositol 3-kinase and Akt activation. Interestingly, supplementation of potassium (8% KCl) ameliorated the changes in insulin sensitivity in Dahl-S rats fed a high-salt diet; this was associated with a slight but significant decrease in blood pressure. Evidence presented suggest that there is an interdependent relationship between insulin sensitivity and salt sensitivity of blood pressure in Dahl-S rats, and it is suggested that supplementing the diet with potassium may exert a protective effect against both hypertension and insulin resistance in salt-sensitive individuals.

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Section: Discussionmentioning

confidence: 99%

High-Salt Diet Enhances Insulin Signaling and Induces Insulin Resistance in Dahl Salt-Sensitive Rats

et al. 2002

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“…Previous findings in genetic hypertensive rats indicate marked interactions between a HSD, increased wall thickness, and increase in Fn. [27][28][29][30] The increase in wall thickness and Fn may contribute to the increase in vascular wall elastic modulus in proportional to the level of circumferential wall stress through an increased number of cell matrix attachments sites. 22 Interestingly, the decrease in MAP in HSD rats treated with valsartan was not associated with a significant reduction in CA wall thickness.…”

Section: Discussionmentioning

confidence: 99%

Effects of Valsartan on Mechanical Properties of the Carotid Artery in Spontaneously Hypertensive Rats Under High-Salt Diet

et al. 2001

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Abstract-The aim of this investigation was to evaluate the influence of a high-salt diet (HSD) on the effects of valsartan, an angiotensin II type 1 (AT 1 ) receptor antagonist, on carotid arterial stiffness and structure in spontaneous hypertensive rats (SHR). Carotid arterial stiffness was studied in SHR receiving a HSD or a normal-salt diet (NSD) from the 10th to 20th week of age. Within each of the 2 groups, the animals received treatment with either placebo or valsartan (30 mg · kg Ϫ1 · d Ϫ1 ) administered on the 4th to 20th week of age. Arterial pressure, wall stress, incremental elastic modulus (Einc), medial cross-sectional area, and EIIIA fibronectin isoform were significantly increased in placebo-HSD rats compared with placebo-NSD rats with no change in the ratio of collagen to elastin. Valsartan reduced mean arterial pressure in both NSD and HSD rats but reduced pulse pressure only in NSD rats. In NSD rats, valsartan reduced Einc and medial cross-sectional area. In HSD, valsartan increased Einc and did not modify medial cross-sectional area and fibronectin. In valsartan-treated rats, the ratio of collagen to elastin was greater in HSD than in NSD rats. In conclusion, the effects of AT 1 blockade are greatly influenced by salt intake in SHR. Despite a reduction in mean arterial pressure in HSD rats, AT 1 blockade was not able to prevent the effects of a HSD on pulse pressure, carotid artery stiffness, and hypertrophy. Key Words: salt Ⅲ angiotensin II Ⅲ AT 1 blockade Ⅲ large artery stiffness Ⅲ carotid artery P revious reports have shown that plasma renin-angiotensin activity is reduced in rats receiving a high-salt diet (HSD). 1-4 However, a long-term HSD in salt-sensitive animals-Dahl salt-sensitive rats, 5 stroke-prone hypertensive rats, 6 -8 or ANP knockout mice 9 -is known to stimulate plasma renin activity. These observations suggest that the effects observed during perturbation of the renin-angiotensin aldosterone system by a high sodium intake may depend on the animal model used. Recently, Wang and Du 10 observed an increased expression of angiotensin II type 1 (AT 1 ) receptor mRNA in arterial preparations derived from Wistar and Sprague-Dawley rats maintained on a HSD. In contrast, when Dahl rats were treated with a HSD, decreases in aortic mRNA and AT 1 receptor density were observed. 5 Together, these results suggested that 1 modification associated with high sodium intake may be at the level of the AT 1 receptor. Interestingly, in spontaneously hypertensive rats (SHR) treated with a HSD, an enhanced functional response to angiotensin II and AT 1 receptor antagonists was demonstrated, suggesting that sodium modified AT 1 activity in SHR. 11,12 Although AT 1 receptor antagonists have been shown to reduce mortality in salt-sensitive animal models (Dahl rats or stroke-prone rats), 7,[13][14][15] there is little evidence available that AT 1 receptor antagonists continually block the elevated blood pressure and arterial abnormalities observed in SHR during high sodium intake.The aim of this inves...

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“…Previous reports have shown that high level of mechanical stress, 15,16 stimulation of the renin angiotensin system, 17,18 as well as high sodium intake 14,19 may stimulate Fn synthesis. Because in these studies the level of wall stress was high, it is difficult to distinguish its role from that of sodium or renin angiotensin system.…”

Section: Arterial Wall Hypertrophy and Compositionmentioning

confidence: 97%

Increased Carotid Wall Elastic Modulus and Fibronectin in Aldosterone-Salt–Treated Rats

et al. 2002

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Background-Previous studies have demonstrated the development of cardiac fibrosis in aldosterone (Aldo)-salt hypertensive rats. Our aim was to determine the effects of Aldo and the Aldo receptor antagonist eplerenone (Epl) on in vivo mechanical properties of the carotid artery using echo-tracking system. Methods and Results-Aldo was administered (1 g/h) in uninephrectomized Sprague-Dawley rats (SD) receiving a high-salt diet from 8 to 12 weeks of age. Uninephrectomized control SD rats received a normal salt diet without Aldo. Three groups of Aldo-salt rats were treated with 1, 10, or 30 mg/kg Ϫ1 · d Ϫ1 of Epl by gavage. Elasticity was measured by elastic modulus (Einc)-wall stress curves using medial cross-sectional area (MCSA). The structure of the arterial wall was analyzed by histomorphometry (elastin and collagen), immunohistochemistry (EIIIA fibronectin, Fn), and Northern blot (collagens I and III). Aldo produced increased systolic arterial pressure, pulse pressure, Einc, MCSA, and EIIIA Fn with no change in wall stress or elastin and collagen densities compared with controls without Aldo. No differences in collagen mRNA levels were detected between groups. Epl blunted the increase in pulse pressure in Aldo rats and normalized Einc-wall stress curves, MCSA, and EIIIA Fn. These effects were dose dependent and not accompanied by a reduction in wall stress. Conclusions-Aldo is able to increase arterial stiffness associated with Fn accumulation, independently of wall stress. The preventive effects of Epl suggest a direct role for mineralocorticoid receptors in mechanical and structural alterations of large vessels in rat hyperaldosteronism.

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Renin–angiotensin system and fibronectin gene expression in Dahl Iwai salt-sensitive and salt-resistant rats

Cited by 31 publications

References 39 publications

High-Salt Diet Enhances Insulin Signaling and Induces Insulin Resistance in Dahl Salt-Sensitive Rats

High-Salt Diet Enhances Insulin Signaling and Induces Insulin Resistance in Dahl Salt-Sensitive Rats

Effects of Valsartan on Mechanical Properties of the Carotid Artery in Spontaneously Hypertensive Rats Under High-Salt Diet

Increased Carotid Wall Elastic Modulus and Fibronectin in Aldosterone-Salt–Treated Rats

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