Possible Mechanisms of Salt-Induced Hypertension in Dahl Salt-Sensitive Rats (original) (raw)
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Its Relevance to Salt-Induced Hypertension in Dahl Rats
2013
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Salt sensitivity in genetically hypertensive rats of the Lyon strain
Kidney International, 2001
Salt sensitivity in genetically hypertensive rats of the Lyon strain. ity is, at least in part, genetically determined, as it is more Background. Genetically hypertensive (LH) rats of the Lyon frequent in black patients [6] and since salt-sensitive rat strain exhibit a blunted pressure-natriuresis function when strains have been developed [3, 4]. However, despite compared, in acute conditions, with their normotensive (LN) intensive efforts, the mechanisms involved remain unand low blood pressure (LL) controls. The present work was known [7-9]. aimed to determine whether LH rats were salt sensitive in chronic conditions. In addition, a protocol was developed to Sodium sensitivity has never been studied in chronic determine the renal function curve in freely moving rats. conditions in the Lyon genetically hypertensive (LH) rats. Methods. Fourteen-week-old rats either untreated or orally Previous acute experiments showed a blunted slope of treated since weaning with perindopril (3 mg/kg/24 h), an angiothe pressure-natriuresis curve [10, 11], which according to tensin-converting enzyme inhibitor, or with valsartan (15 mg/kg/ Guyton's study determines the BP response to increased 24 h), an angiotensin II subtype 1 receptor antagonist, so as to eliminate the influence of endogenous changes in angiotensin salt intake [12], thus suggesting that LH rats should be formation were used. Blood pressure (BP) and urinary sodium salt sensitive in addition of being spontaneously hyperexcretion were measured before, during an oral salt load (2% tensive. However, since it is difficult to extrapolate from NaCl in drinking water), and during a two-week aldosterone acute studies in anesthetized rats to chronic situations, infusion (50 g/kg/24 h subcutaneously). Results. NaCl induced a greater BP increase in untreated
Salt-induced hypertension in normotensive spontaneously hypertensive rats
…, 1994
Lifetime treatment with oral captopril prevents the development of hypertension in spontaneously hypertensive rats (SHR). We tested the hypothesis that this treatment also prevents the hypertensive response that occurs when untreated NaCl-sensitive SHR are placed on a high NaCl diet. Female SHR were continuously treated with oral captopril before conception and throughout lactation, and the offspring were similarly treated with oral captopril throughout life. At 6 weeks of age, treated male SHR were placed on an 8% (or remained on a 1%) NaCl diet, and systolic arterial pressure, heart rate, and body weight were monitored for 2 weeks. The 8% NaCl diet caused a rapid increase in arterial pressure in the lifetime captopril-treated rats, and 18 days after the initiation of the diet, the mean arterial pressure of this group was 136±7 mm Hg compared with 100±2 mm Hg in the 1% NaCl diet rats. The results of a second experiment confirmed the hypertensive effect of the high NaCl diet in lifetime captopril-treated SHR and demonstrated that after 18 days on
Differential sympathetic and angiotensinergic responses in rats submitted to low- or high-salt diet
Regulatory Peptides, 2007
The present study was designed to evaluate, in Wistar rats, the effect of high- or low-salt diet on the hemodynamic parameters and on the renal and lumbar sympathetic nerve activity. The renal gene expression of the renin angiotensin system components was also evaluated, aiming to find some correlation between salt intake, sodium homeostasis and blood pressure increase. Male Wistar rats received low (0.06% Na, TD 92141-Harlan Teklad), a normal (0.5% Na, TD 92140), or a high-salt diet (3.12% Na, TD 92142) from weaning to adulthood. Hemodynamic parameters such as cardiac output and total peripheral resistance, and the renal and lumbar sympathetic nerve activity were determined (n=45). Plasma renin activity, plasma and renal content of angiotensin (ANG) I and II, and the renal mRNA expression of angiotensinogen, renin, AT1 and AT2 receptors were also measured (n=24). Compared to normal- and low-salt diet-, high-salt-treated rats were hypertensive and developed an increase (P<0.05) in total peripheral resistance and lumbar sympathetic nerve activity. A decrease in renal renin and angiotensinogen-mRNAs and in plasma ANG II and plasma renin activity was also found in salt overloaded animals. The renal sympathetic nerve activity was higher (P<0.05) in low- compared to high-salt-treated rats, and was associated with an increase (P<0.05) in renal ANG I and II and with a decrease (P<0.05) in AT2 renal mRNA. Plasma ANG I and II and plasma renin activity were higher in low- than in normal-salt rats. Our results show that increased blood pressure is associated with increases in lumbar sympathetic nerve activity and total peripheral resistance in high-salt-treated rats. However, in low-salt-treated rats an increase in the renal sympathetic nerve was correlated with an increase in the renal content of ANG I and II and with a decrease in AT2 renal mRNA. These changes are probably in favor of the antinatriuretic response and the sodium homeostasis in the low-salt group.
Mechanisms of Salt-Sensitive Hypertension
Current Hypertension Reviews, 2015
Hypertension and its consequences, including heart failure, stroke, and kidney disease, are responsible for substantial morbidity and mortality worldwide. Lifestyle changes, particularly sodium reduction, contribute to blood pressure control. However, not all individuals, whether normotensive or hypertensive, have the same susceptibility to the effects of salt. While a variety of approaches have been proposed to identify salt sensitive patients, there is no consensus for a definition of salt sensitivity and the precise mechanisms that explain their association are not yet fully understood. In this review we summarize the current understanding of the various pathophysiological mechanisms potentially involved in determining the salt sensitive phenotype. Genetic, neuronal, and immune alterations are reviewed. Additionally, we provide an update on the current knowledge of a new approach proposing the interstitium of the skin may act as a sodium reservoir. The role of dietary potassium on salt sensitive hypertension is also summarized.
Journal of the American Heart Association, 2021
Background Abnormal renal hemodynamic responses to salt‐loading are thought to contribute to salt‐sensitive (SS) hypertension. However, this is based largely on studies in anesthetized animals, and little data are available in conscious SS and salt‐resistant rats. Methods and Results We assessed arterial blood pressure, renal function, and renal blood flow during administration of a 0.4% NaCl and a high‐salt (4.0% NaCl) diet in conscious, chronically instrumented 10‐ to 14‐week‐old Dahl SS and consomic SS rats in which chromosome 1 from the salt‐resistant Brown‐Norway strain was introgressed into the genome of the SS strain (SS.BN1). Three weeks of high salt intake significantly increased blood pressure (20%) and exacerbated renal injury in SS rats. In contrast, the increase in blood pressure (5%) was similarly attenuated in Brown‐Norway and SS.BN1 rats, and both strains were completely protected against renal injury. In SS.BN1 rats, 1 week of high salt intake was associated with a ...
Salt Sensitivity and Hypertension
Hypertension Journal, 2017
Enough evidence is there to link excess salt intake with cardiovascular and renal risks through hypertension though substantial evidence is also there to support that blood pressure is not always responding to salt. A lot of metabolic and neurohormonal factors determine this salt sensitivity in addition to genetic factors that determine substantial excretion of salt, so it may not increase blood pressure despite high intake. Salt-sensitive hypertensives have reduced levels of urinary endothelin, contributing to impaired natriuresis in response to a salt load. Salt load also increases free radicals and paradoxically decreases excretion of nitric oxide metabolites in salt-sensitive individuals. Type 2 diabetic patients with microalbuminuria are more salt sensitive as they have lower urinary excretion of nitric oxide. Nitric oxide deficiency facilitates endothelial dysfunction causing hypertension in salt-sensitive people, impeding vasodilation after salt load. Sympathetic nervous system plays a significant role in maintenance of blood pressure in response to salt through urinary and plasma levels of catecholamine and renal nerve activity. Apart from this, atrial natriuretic peptides (ANPs) and cytochrome P450-derived metabolites of arachidonic acid play significant roles. Insomnia and menopause increase salt sensitivity. Kidney provides sensitive and specific biomarkers for salt sensitivity in the form of proteomics, and renal proximal tubule cells, microribonucleic acid (miRNA), and exosomes are excreted into the urine apart from genetic biomarkers. A J-shaped curve relationship exists between salt intake and mortality. Salt intakes above and below the range of 2.5 to 6.0 gm/day are associated with high cardiovascular risk. Salt restriction can be a cause of hypertension in inverse salt-sensitive people. Available prevalence studies do not differentiate between salt-sensitive and salt-resistant populations, nor do they include normotensive salt-sensitive people who get their blood pressure raised in response to dietary salt. In these circumstances, salt sensitivity arises as an independent risk factor for cardiovascular mortality and morbidity.
Hypertension Research, 2008
High salt intake increases blood pressure (BP) in spontaneously hypertensive rats (SHR), and central neural mechanisms are suggested to be involved. Increased generation of reactive oxygen species (ROS) in the rostral ventrolateral medulla (RVLM) contributes to the neural mechanism of hypertension in SHR. We sought to examine whether high salt intake increases hypertension in SHR and whether the increased ROS in the RVLM contributes to this mechanism. Male SHR and Wistar-Kyoto rats (WKY) (6 weeks old) were fed a high-salt diet (8%: HS-S; HS-W) or a regular-salt diet (0.5%: RS-S; RS-W) for 6 weeks. Systolic BP was significantly higher in HS-S than in RS-S at 12 weeks of age (244 ± 5 vs. 187 ± 7 mmHg, n =8; p <0.05). Urinary norepinephrine excretion was significantly higher in HS-S than in RS-S. Thiobarbituric acid-reactive substances levels in the RVLM were significantly higher in HS-S than in RS-S (9.9 ± 0.5 vs. 8.1 ± 0.6 µmol/g wet wt, n =5; p<0.05). Microinjection of tempol or valsartan into the RVLM induced significantly greater BP reduction in HS-S than in RS-S. The increase in angiotensin II type 1 receptor (AT1R) expression and the increase in reduced nicotinamide-adenine dinucleotide phosphate (NAD(P)H) oxidase activity in the RVLM were significantly greater in HS-S than in RS-S. These findings indicate that high salt intake exacerbates BP elevation and sympathetic nervous system activity during the development of hypertension in SHR. These responses are mediated by increased ROS generation that is probably due to upregulation of AT1R/NAD(P)H oxidase in the RVLM.
24-hour blood pressure recordings in Dahl rats on high- and low-salt diets
The American journal of physiology, 1989
The goal of this study was to determine if the baroreflex abnormality previously shown in Dahl-sensitive (DS) rats would increase blood pressure and heart rate (HR) variability. Mean arterial pressure (MAP) and HR were sampled every 2 s for 24 h from Dahl-resistant (DR) and DS rats on low- and high-salt diets (n = 12-13 in each group). MAP +/- SD was significantly elevated in the DS rats on high-salt diets (DSH); the SD of MAP in the DSH rats was also significantly higher compared with similar measurements in rats on high-salt diets (DRH) and DS rats on low-salt diets (DSL) when SD was divided by MAP. MAP was higher at night than during the day in the DSH rats. In contrast, HR and HR variability were not significantly different between the groups. The baroreflex control of HR, determined by means of graded injections of phenylephrine, was least in the DSH rats and increased, respectively, with DSL rats, DRH rats, and DR rats on low-salt diets. There was no significant correlation be...