Mapping and confirmation of a major left ventricular mass QTL on rat chromosome 1 by contrasting SHRSP and F344 rats

2013 ◽  
Vol 45 (18) ◽  
pp. 827-833 ◽  
Author(s):  
Katja Grabowski ◽  
Gerold Koplin ◽  
Bujar Aliu ◽  
Leonard Schulte ◽  
Angela Schulz ◽  
...  
Keyword(s):  
Salt Intake ◽  
Target Organ Damage ◽  
Left Ventricular ◽  
High Salt ◽  
Chromosome 1 ◽  
Dietary Salt ◽  
A Genome ◽  
High Salt Intake ◽  
Lv Mass ◽  
Major Qtl

An abnormal increase in left ventricular (LV) mass, i.e., LV hypertrophy (LVH), represents an important target organ damage in arterial hypertension and has been associated with poor clinical outcome. Genetic factors are contributing to variation in LV mass in addition to blood pressure and other factors such as dietary salt intake. We set out to map quantitative trait loci (QTL) for LV mass by comparing the spontaneously hypertensive stroke-prone (SHRSP) rat with LVH and normotensive Fischer rats (F344) with contrasting low LV mass. To this end we performed a genome-wide QTL mapping analysis in 232 F2 animals derived from SHRSP and F344 exposed to high-salt (4% in chow) intake for 8 wk. We mapped one major QTL for LV mass on rat chromosome 1 (RNO1) that demonstrated strong linkage (peak logarithm of odds score 8.4) to relative LV weight (RLVW) and accounted for ∼19% of the variance of this phenotype in F2 rats. We therefore generated a consomic SHRSP-1F344 strain in which RNO1 from F344 was introgressed into the SHRSP background. Consomic and SHRSP animals showed similar blood pressures during conventional intra-arterial measurements, while RLVW was already significantly lower (−17.7%, P < 0.05) in SHRSP-1F344 in response to a normal-salt diet; a similar significant reduction of LV mass was also observed in consomic rats after high-salt intake ( P < 0.05 vs. SHRSP). Thus, a major QTL on RNO1 was confirmed with significant impact on LV mass in the hypertensive background of SHRSP.

Links Between Dietary Salt Intake, Renal Salt Handling, Blood Pressure, and Cardiovascular Diseases

2005 ◽  
Vol 85 (2) ◽  
pp. 679-715 ◽  
Author(s):  
Pierre Meneton ◽  
Xavier Jeunemaitre ◽  
Hugh E. de Wardener ◽  
Graham A. Macgregor
Keyword(s):  
Blood Pressure ◽  
Cardiovascular Diseases ◽  
Salt Intake ◽  
Causal Link ◽  
Left Ventricular ◽  
High Salt ◽  
Human Populations ◽  
Dietary Salt ◽  
Dietary Salt Intake ◽  
High Salt Intake

Epidemiological, migration, intervention, and genetic studies in humans and animals provide very strong evidence of a causal link between high salt intake and high blood pressure. The mechanisms by which dietary salt increases arterial pressure are not fully understood, but they seem related to the inability of the kidneys to excrete large amounts of salt. From an evolutionary viewpoint, the human species is adapted to ingest and excrete <1 g of salt per day, at least 10 times less than the average values currently observed in industrialized and urbanized countries. Independent of the rise in blood pressure, dietary salt also increases cardiac left ventricular mass, arterial thickness and stiffness, the incidence of strokes, and the severity of cardiac failure. Thus chronic exposure to a high-salt diet appears to be a major factor involved in the frequent occurrence of hypertension and cardiovascular diseases in human populations.

AT1receptor antagonism attenuates target organ effects of salt excess in SHRs without affecting pressure

2008 ◽  
Vol 294 (2) ◽  
pp. H853-H858 ◽  
Author(s):  
Jasmina Varagic ◽  
Edward D. Frohlich ◽  
Dinko Susic ◽  
Jwari Ahn ◽  
Luis Matavelli ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Arterial Pressure ◽  
Myocardial Fibrosis ◽  
Salt Intake ◽  
Target Organ Damage ◽  
Organ Damage ◽  
Left Ventricular ◽  
Target Organ ◽  
Dietary Salt ◽  
High Salt Intake

Our recent studies have demonstrated that salt excess in the spontaneously hypertensive rat (SHR) produces a modestly increased arterial pressure while promoting marked myocardial fibrosis and structural damage associated with altered coronary hemodynamics and ventricular function. The present study was designed to determine the efficacy of an angiotensin II type 1 (AT1) receptor blocker (ARB) in the prevention of pressure increase and development of target organ damage from high dietary salt intake. Eight-week-old SHRs were given an 8% salt diet for 8 wk; their age- and gender-matched controls received standard chow. Some of the salt-loaded rats were treated concomitantly with ARB (candesartan; 10 mg·kg−1·day−1). The ARB failed to reduce the salt-induced rise in pressure, whereas it significantly attenuated left ventricular (LV) remodeling (mass and wall thicknesses), myocardial fibrosis (hydroxyproline concentration and collagen volume fraction), and the development of LV diastolic dysfunction, as shown by longer isovolumic relaxation time, decreased ratio of peak velocity of early to late diastolic waves, and slower LV relaxation (minimum first derivative of pressure over time/maximal LV pressure). Without affecting the increased pulse pressure by high salt intake, the ARB prevented the salt-induced deterioration of coronary and renal hemodynamics but not the arterial stiffening or hypertrophy (pulse wave velocity and aortic mass index). Additionally, candesartan prevented the salt-induced increase in kidney mass index and proteinuria. In conclusion, the ARB given concomitantly with dietary salt excess ameliorated salt-related structural and functional cardiac and renal abnormalities in SHRs without reducing arterial pressure. These data clearly demonstrated that angiotensin II (via AT1receptors), at least in part, participated importantly in the pressure-independent effects of salt excess on target organ damage of hypertension.

Prevalence, Biochemical and Clinical Characteristics of Resistant Hypertension

2018 ◽  
Vol 69 (10) ◽  
pp. 2845-2849
Author(s):  
Daniela Gurgus ◽  
Elena Ardeleanu ◽  
Carmen Gadau ◽  
Roxana Folescu ◽  
Ioan Tilea ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Cardiovascular Disease ◽  
Resistant Hypertension ◽  
Clinical Characteristics ◽  
Salt Intake ◽  
Target Organ Damage ◽  
Multivariate Logistic Regression Analysis ◽  
Organ Damage ◽  
Left Ventricular ◽  
High Salt Intake

The objectives of the present study were to evaluate the prevalence of resistant hypertension (RH) in primary care setting and to analyse its biochemical and clinical characteristics. After 3 months of treatment and evaluation, 721 (14.01%) of 5,146 patients with hypertension did not reach target office blood pressure of [ 140/90 mmHg. After exclusion of �white-coat effect� with ambulatory blood pressure, of secondary and pseudo- resistant hypertension, prevalence of RH was 6.74%. Lifestyle factors associated with RH were physical inactivity, obesity, high salt intake, smoking and excessive alcohol ingestion. Compared to controlled hypertension, RH patients presented higher incidence of family history of cardiovascular disease (38.90% vs 25.94%), diabetes mellitus (34.87% vs 19.01%), impaired fasting glucose (21.91% vs 19.07%), target organ damage (29.1% vs 15.95%), and cardiovascular disease (27.09% vs 17.06%). Dyslipidaemia (52.90% vs 42.03%), fasting plasma glucose (116.10�38.9 vs 107.80�37.2), HbA1c (6.41�1.42 vs 5.96�0.94), serum creatinine (1.09�0.27 vs 1.03�0.24) and microalbuminuria (21.90% vs 10.95%) were significantly higher in RH. Predictors of RH, determined by a multivariate logistic regression analysis were left ventricular hypertrophy (OD 2.14, 95% CI 1.32-3.69), renal impairment expressed as eGFR [ 60 ml/min/1.73m2 (OD 1.62, 95% CI 1.21-2.21) and the presence of cardiovascular disease (OD 1.48, 95% CI 1.02-2.16).

Limitation of arteriolar myogenic activity by local nitric oxide: segment-specific effect of dietary salt

1999 ◽  
Vol 277 (5) ◽  
pp. H1946-H1955 ◽  
Author(s):  
Timothy R. Nurkiewicz ◽  
Matthew A. Boegehold
Keyword(s):  
Nitric Oxide ◽  
Salt Intake ◽  
Specific Effect ◽  
High Salt ◽  
Myogenic Response ◽  
Dietary Salt ◽  
No Donor ◽  
Spontaneously Hypertensive ◽  
High Salt Intake ◽  
Wistar Kyoto

The purpose of this study was to determine if local nitric oxide (NO) activity attenuates the arteriolar myogenic response in rat spinotrapezius muscle. We also investigated the possibility that hypertension, dietary salt, or their combination can alter any influence of local NO on the myogenic response. Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) fed low-salt (0.45%, LS) or high-salt (7%, HS) diets were enclosed in a ventilated airtight box with the spinotrapezius muscle exteriorized for intravital microscopy. Mean arterial pressure was unaffected by dietary salt in WKY but was significantly higher and augmented by dietary salt in SHR. In all experiments, elevation of microvascular pressure by box pressurization caused a 0–30% decrease in the diameter of large (arcade bridge) arterioles and a 21–27% decrease in the diameter of intermediate (arcade) arterioles. Inhibition of NO synthase with N G-monomethyl-l-arginine (l-NMMA) significantly enhanced myogenic responsiveness of arcade bridge arterioles in WKY-LS and SHR-LS but not in WKY-HS and SHR-HS.l-NMMA significantly enhanced the myogenic responsiveness of arcade arterioles in all four groups. Excess l-arginine reversed this effect of l-NMMA in all cases, and arteriolar responsiveness to the NO donor sodium nitroprusside was not different among the four groups. High-salt intake had no effect on the passive distension of arterioles in either strain during box pressurization. We conclude that 1) local NO normally attenuates arteriolar myogenic responsiveness in WKY and SHR, 2) dietary salt impairs local NO activity in arcade bridge arterioles of both strains, and 3) passive arteriolar distensibility is not altered by a high-salt diet in either strain.

scholarly journals High Salt Intake Increases Copeptin but Salt Sensitivity Is Associated with Fluid Induced Reduction of Copeptin in Women

2014 ◽  
Vol 2014 ◽  
pp. 1-5 ◽  
Author(s):  
Irina Tasevska ◽  
Sofia Enhörning ◽  
Philippe Burri ◽  
Olle Melander
Keyword(s):  
Body Weight ◽  
Salt Intake ◽  
Salt Sensitivity ◽  
High Salt ◽  
Dietary Salt ◽  
Urinary Volume ◽  
Salt Consumption ◽  
High Salt Intake ◽  
Low Salt ◽  
Induced Changes

This study investigated if copeptin is affected by high salt intake and whether any salt-induced changes in copeptin are related to the degree of salt sensitivity. The study was performed on 20 men and 19 women. In addition to meals containing 50 mmol NaCl daily, capsules containing 100 mmol NaCl and corresponding placebo capsules were administered during 4 weeks each, in random order. Measurements of 24 h blood pressure, body weight, 24 h urinary volume, and fasting plasma copeptin were performed at high and low salt consumption. Copeptin increased after a high compared to low dietary salt consumption in all subjects 3,59 ± 2,28 versus 3,12 ± 1,95 (P= 0,02). Copeptin correlated inversely with urinary volume, at both low (r= −0,42;P= 0,001) and high (r= −0,60;P< 0,001) salt consumption, as well as with the change in body weight (r= −0,53;P< 0,001). Systolic salt sensitivity was inversely correlated with salt-induced changes of copeptin, only in females (r= −0,58;P= 0,017). As suppression of copeptin on high versus low salt intake was associated with systolic salt sensitivity in women, our data suggest that high fluid intake and fluid retention may contribute to salt sensitivity.

Altered peripheral noradrenergic activity in intact and sinoaortic denervated Dahl rats

1989 ◽  
Vol 67 (5) ◽  
pp. 442-449 ◽  
Author(s):  
J. D. Peuler ◽  
K. P. Patel ◽  
D. A. Morgan ◽  
C. A. Whiteis ◽  
D. D. Lund ◽  
...  
Keyword(s):  
Sympathetic Activity ◽  
Sinoatrial Node ◽  
Renal Cortex ◽  
Salt Intake ◽  
Left Ventricular ◽  
High Salt ◽  
Arterial Baroreflex ◽  
High Salt Intake ◽  
Cardiac Ventricle ◽  
Cardiac Ventricles

Development of salt-induced hypertension in Dahl salt-sensitive (S) rats is dependent on sympathetic overactivity which may be partially related to arterial baroreflex dysfunction and, therefore, is regionally selective. Our first experiment was designed to determine which regions have elevated sympathetic activity in Dahl S compared with Dahl salt-resistant (R) rats. Weanling (4-week-old) female Dahl R and S rats were fed low or high salt diets (0.13% and 8% NaCl) until 10 weeks of age. Norepinephrine (NE) synthesis was blocked with α-methyl-p-tyrosine, and the fractional decline of NE concentration was measured in various tissues. Dahl S rats with increases in both arterial pressure and left ventricular weight demonstrated increased NE turnover in the sinoatrial node, the atrial appendages, the cardiac ventricles, and the renal cortex. In all of these tissues except the cardiac ventricle, increases were associated with high salt intake. Our second experiment was designed to test if arterial baroreflex dysfunction could account for regional increases in sympathetic activity. Separate groups of Dahl R and S rats fed high salt were subjected to either sham surgery or sinoaortic baroreceptor denervation 1 week prior to turnover determinations. Sinoaortic baroreceptor denervation abolished differences in NE turnover between salt-fed Dahl R and S rats in the cardiac sinoatrial node and the atrial appendages, but not in the cardiac ventricles and the renal cortex. Sinoaortic baroreceptor denervation also abolished differences between salt-fed Dahl S and R rats in the spleen but not the duodenum. Thus in awake, undisturbed Dahl S rats, sympathetic activity may be increased in the cardiac ventricles, regardless of salt intake. High salt intake may induce elevated sympathetic activity in the renal cortex and in the cardiac atria and sinoatrial node of Dahl S but not R rats. Sinoaortic baroreflex dysfunction in Dahl S rats may contribute to some, but not all, regional increases in sympathetic activity.Key words: high salt intake, hypertension, cardiac hypertrophy, norepinephrine turnover, sympathetic activity, sinoaortic denervation.

Abstract P150: Aldosterone Dysregulation Increases Cardiovascular Risk in African-American Youth

Circulation ◽  
2012 ◽  
Vol 125 (suppl_10) ◽  
Author(s):  
Gregory A Harshfield ◽  
Evan Mulloy ◽  
Melinda Beavers
Keyword(s):  
Blood Pressure ◽  
Cardiovascular Disease ◽  
African American ◽  
African Americans ◽  
Early Development ◽  
Salt Intake ◽  
Target Organ Damage ◽  
Target Organ ◽  
High Salt ◽  
High Salt Intake

Background: The prevalence of hypertension and blood pressure-related target organ damage in African-Americans is among the highest in the world. We hypothesize that this is in part due to aldosterone dysregulation among African-Americans beginning in youth and leading to the early development of cardiovascular disease in this population. To begin to test this hypothesis, we examined ethnic differences in aldosterone regulation in normal, healthy adolescents. Methods: The subjects in this study were 145 (60 Caucasian, 85 African-American) healthy, normotensive youth aged 15–19 years. Testing was performed following 72 hours on a controlled sodium diet. Testing consisted of the collection of aldosterone, systolic blood pressure (SBP), and urinary sodium excretion (U Na V) during continuous water intake (400 ml total) over a 2 hour period. An echocardiogram was also performed to measure target organ changes. Log transformations were performed on aldosterone levels prior to analyses. Results: African-American compared to Caucasian subjects had higher casual SBP (109±10 v 104±10; p=.006) and relative wall thickness (0.32±.03 v 0.34±.04; p=.003). During the testing procedure African-Americans also had lower levels of aldosterone (4.78±.6 v 4.35±.6 pg/ml; p =.001). In the Caucasian subjects only, aldosterone was inversely correlated with U Na V (r=−0.427; p=.001) and U Na V was positively correlated with SBP (r=0.356; p=.001). The subjects were divided into those in the upper and lower quartiles of salt intake for further analysis. The interaction between race and salt intake was significant for aldosterone (F=7.173; p=.008). Caucasian subjects with high salt intake had lower aldosterone (4.56±.59 v 5.02±0.59 pg/ml). However, aldosterone levels did not differ by salt intake in African-Americans. Summary and Conclusion: African-American subjects did not show the expected associations between aldosterone and the pressure natriuresis relation. Furthermore, African-Americans on the high salt intake failed to suppress aldosterone. These findings are consistent with our hypothesis that aldosterone dysregulation in youth may lead to the early development of cardiovascular disease in Africans-Americans.

A high-salt diet does not influence renal sympathetic nerve activity: a direct telemetric investigation

2009 ◽  
Vol 297 (2) ◽  
pp. R396-R402 ◽  
Author(s):  
Fiona D. McBryde ◽  
Simon C. Malpas ◽  
Sarah-Jane Guild ◽  
Carolyn J. Barrett
Keyword(s):  
Sympathetic Nerve Activity ◽  
Salt Intake ◽  
High Salt ◽  
Ang Ii ◽  
Dietary Salt ◽  
Nerve Activity ◽  
Renal Sympathetic Nerve Activity ◽  
Salt Diet ◽  
High Salt Intake ◽  
Renal Sympathetic

The importance of dietary salt in the development of hypertension has long been a source of controversy. Recent studies suggest a combination of high-salt and ANG II infusion may increase sympathetic drive; however, the effect of a change in dietary salt alone is unclear. Using telemetry, we recorded renal sympathetic nerve activity (RSNA), arterial pressure (MAP), and heart rate (HR) in seven New Zealand white rabbits before and during a 6-day period of increased salt intake (normal NaCl 0.5 g·kg−1·day−1, high NaCl 2.5 g·kg−1·day−1) and a second group of seven rabbits with normal salt intake throughout. The responses to stressful stimuli encountered in the laboratory were recorded and compared with rest in control and high-salt groups. Resting MAP, HR, and RSNA were not significantly altered with high salt intake [88 ± 5 vs. 91 ± 6 mmHg; 251 ± 8 vs. 244 ± 9 beats per minute (bpm); 9.7 ± and 1.2 vs. 10.8 ± 1.7 normalized units (nu)] despite significant reductions in plasma renin activity (1.88 ± 0.18 vs. 1.27 ± 0.15 nmol ANG I·l−1·h−1; P < 0.05) and ANG II (7.5 ± 1.2 vs. 4.3 ± 0.8 pmol/l). Increasing levels of stressful stimuli (resting in home cage, containment in box, handling, and nasopharyngeal activation) in animals on a normal salt diet caused graded increases in MAP (89 ± 2 mmHg, 95 ± 2 mmHg, 107 ± 4 mmHg, and 122 ± 5 mmHg, respectively) and RSNA (9.7 ± 0.9 nu; 11.8 ± 2.7 nu; 31.4 ± 3.7 nu; 100 nu) but not HR (245 ± 8 bpm; 234 ± 8 bpm; 262 ± 9 bpm; 36 ± 5 bpm). High dietary salt did not significantly alter the responses to stress. We conclude that a 6-day period of high salt intake does not alter the level of RSNA, with non-neural mechanisms primarily responsible for the observed renin-angiotensin system suppression.

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