On average, black individuals are widely believed to be more sensitive than white individuals to blood pressure (BP) effects of changes in salt intake. However, few studies have directly compared the BP effects of changing salt intake in black versus white individuals. In this narrative review, we analyze those studies and note that when potassium intake substantially exceeds the recently recommended US dietary goal of 87 mmol/day, black adults do not appear more sensitive than white adults to BP effects of short-term or long-term increases in salt intake (from an intake ≤50 mmol/day up to 150 mmol/day or more). However, with lower potassium intakes, racial differences in salt sensitivity are observed. Mechanistic studies suggest that racial differences in salt sensitivity are related to differences in vascular resistance responses to changes in salt intake mediated by vasodilator and vasoconstrictor pathways. With respect to cause and prevention of racial disparities in salt sensitivity, it is noteworthy that 1) on average, black individuals consume less potassium than white individuals and 2) consuming supplemental potassium bicarbonate, or potassium rich foods can prevent racial disparities in salt sensitivity. However, the new US dietary guidelines reduced the dietary potassium goal well below the amount associated with preventing racial disparities in salt sensitivity. These observations should motivate research on the impact of the new dietary potassium guidelines on racial disparities in salt sensitivity, the risks and benefits of potassium-containing salt substitutes or supplements, and methods for increasing consumption of foods rich in nutrients that protect against salt-induced hypertension.
- MeSH
- běloši MeSH
- černoši MeSH
- draslík dietní * MeSH
- hypertenze patofyziologie MeSH
- krevní tlak fyziologie MeSH
- lidé MeSH
- rizikové faktory MeSH
- sodík dietní * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Research Support, N.I.H., Extramural MeSH
- MeSH
- chlorid sodný * MeSH
- krevní tlak MeSH
- kuchyňská sůl * MeSH
- měření krevního tlaku MeSH
- Publikační typ
- časopisecké články MeSH
- komentáře MeSH
Common inbred strains of the laboratory rat can be divided into four major mitochondrial DNA (mtDNA) haplotype groups represented by the BN, F344, LEW, and SHR strains. In the current study, we investigated the metabolic and hemodynamic effects of the SHR vs. F344 mtDNA by comparing the SHR vs. SHR-mt(F344) conplastic strains that are genetically identical except for their mitochondrial genomes. Altogether 13 amino acid substitutions in protein coding genes, seven single nucleotide polymorphisms in tRNA genes, and 12 single nucleotide changes in rRNA genes were detected in F344 mtDNA compared with SHR mtDNA. Analysis of oxidative phosphorylation system (OXPHOS) in heart left ventricles (LV), muscle, and liver revealed reduced activity and content of several respiratory chain complexes in SHR-mt(F344) conplastic rats compared with the SHR strain. Lower function of OXPHOS in LV of conplastic rats was associated with significantly increased relative ventricular mass and reduced fractional shortening that was independent of blood pressure. In addition, conplastic rats exhibited reduced sensitivity of skeletal muscles to insulin action and impaired glucose tolerance. These results provide evidence that inherited alterations in mitochondrial genome, in the absence of variation in the nuclear genome and other confounding factors, predispose to insulin resistance, cardiac hypertrophy and systolic dysfunction.
- MeSH
- adeninnukleotidy metabolismus MeSH
- elektrokardiografie MeSH
- fenotyp MeSH
- funkce levé komory srdeční účinky léků MeSH
- genová dávka MeSH
- glukosa metabolismus MeSH
- glukózový toleranční test MeSH
- haplotypy genetika MeSH
- inzulin farmakologie MeSH
- inzulinová rezistence genetika MeSH
- kardiomegalie genetika patofyziologie MeSH
- krevní tlak účinky léků MeSH
- metabolismus lipidů účinky léků MeSH
- mitochondriální DNA genetika MeSH
- mitochondriální geny MeSH
- molekulární sekvence - údaje MeSH
- oxidativní fosforylace * účinky léků MeSH
- potkani inbrední F344 MeSH
- potkani inbrední SHR MeSH
- RNA transferová genetika MeSH
- sekvence nukleotidů MeSH
- sekvenční analýza DNA MeSH
- systola * účinky léků MeSH
- transport elektronů účinky léků MeSH
- velikost orgánu účinky léků MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
CD36 fatty acid translocase plays a key role in supplying heart with its major energy substrate, long-chain fatty acids (FA). Previously, we found that the spontaneously hypertensive rat (SHR) harbors a deletion variant of Cd36 gene that results in reduced transport of long-chain FA into cardiomyocytes and predisposes the SHR to cardiac hypertrophy. In the current study, we analyzed the effects of mutant Cd36 on susceptibility to ischemic ventricular arrhythmias and myocardial infarction in adult SHR-Cd36 transgenic rats with wild-type Cd36 compared with age-matched SHR controls. Using an open-chest model of coronary artery occlusion, we found that SHR-Cd36 transgenic rats showed profound arrhythmogenesis resulting in significantly increased duration of tachyarrhythmias (207 ± 48 s vs. 55 ± 21 s, P < 0.05), total number of premature ventricular complexes (2,623 ± 517 vs. 849 ± 250, P < 0.05) and arrhythmia score (3.86 ± 0.18 vs. 3.13 ± 0.13, P < 0.001). On the other hand, transgenic SHR compared with SHR controls showed significantly reduced infarct size (52.6 ± 4.3% vs. 72.4 ± 2.9% of area at risk, P < 0.001). Similar differences were observed in isolated perfused hearts, and the increased susceptibility of transgenic SHR to arrhythmias was abolished by reserpine, suggesting the involvement of catecholamines. To further search for possible molecular mechanisms of altered ischemic tolerance, we compared gene expression profiles in left ventricles dissected from 6-wk-old transgenic SHR vs. age-matched controls using Illumina-based sequencing. Circadian rhythms and oxidative phosphorylation were identified as the top KEGG pathways, while circadian rhythms, VDR/RXR activation, IGF1 signaling, and HMGB1 signaling were the top IPA canonical pathways potentially important for Cd36-mediated effects on ischemic tolerance. It can be concluded that transgenic expression of Cd36 plays an important role in modulating the incidence and severity of ischemic and reperfusion ventricular arrhythmias and myocardial infarct size induced by coronary artery occlusion. The proarrhythmic effect of Cd36 transgene appears to be dependent on adrenergic stimulation.
- MeSH
- antigeny CD36 genetika metabolismus MeSH
- genetická predispozice k nemoci MeSH
- infarkt myokardu genetika metabolismus patologie MeSH
- krevní tlak MeSH
- krysa rodu rattus MeSH
- potkani inbrední SHR MeSH
- srdeční arytmie genetika metabolismus MeSH
- stanovení celkové genové exprese MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
In the HXB and BXH recombinant inbred strains derived from the spontaneously hypertensive rat and the normotensive Brown Norway rat, we determined the strain distribution patterns of 500 genetic markers to scan the rodent genome for quantitative trait loci regulating cardiac mass and blood pressure. The markers spanned approximately 1,139 cM of the genome and were tested for correlations with left ventricular mass adjusted for body weight, and with systolic, diastolic, and mean arterial pressures. The marker for the dopamine 1A receptor (Drd1a) on chromosome 17 showed the strongest correlation with left ventricular heart weight (P = .00038, r = -0.59) and the relationship to heart weight was independent of blood pressure. The markers showing the strongest correlations with systolic, diastolic, and mean arterial pressure were D19Mit7 on chromosome 19 (P = .0012, r = .55), D2N35 on chromosome 2 (P = .0008, r = .56), and Il6 on chromosome 4 (P = .0018, r = .53), respectively. These studies demonstrate that the HXB and BXH strains can be effectively used for genome scanning studies of complex traits and have revealed several chromosome regions that may be involved in the genetic control of blood pressure and cardiac mass in the rat.
- MeSH
- hypertenze * genetika MeSH
- krevní tlak * MeSH
- krysa rodu rattus MeSH
- mapování chromozomů * MeSH
- potkani inbrední BN MeSH
- potkani inbrední SHR MeSH
- rekombinace genetická MeSH
- srdce * anatomie a histologie MeSH
- velikost orgánu MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- práce podpořená grantem MeSH
- Research Support, U.S. Gov't, P.H.S. MeSH
- MeSH
- alkalická fosfatasa * genetika MeSH
- antigeny CD45 * genetika MeSH
- druhová specificita MeSH
- geny * MeSH
- inbrední kmeny potkanů MeSH
- inhibiny * genetika MeSH
- křížení genetické MeSH
- krysa rodu rattus * genetika MeSH
- krystaliny * genetika MeSH
- lidé MeSH
- lod skóre MeSH
- mapování chromozomů MeSH
- myši genetika MeSH
- potkani inbrední LEW MeSH
- potkani inbrední SHR MeSH
- proteinfosfatasa 1 MeSH
- renin * genetika MeSH
- sodíko-draslíková ATPasa * genetika MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus * genetika MeSH
- lidé MeSH
- myši genetika MeSH
- zvířata MeSH
- Publikační typ
- srovnávací studie MeSH
