scholarly journals Sex-specific differences in chromosome-dependent regulation of vascular reactivity in female consomic rat strains from a SS × BN cross

2008 ◽  
Vol 295 (2) ◽  
pp. R516-R527 ◽  
Author(s):  
Mary Pat Kunert ◽  
Melinda R. Dwinell ◽  
Ines Drenjancevic Peric ◽  
Julian H. Lombard

High-throughput studies in the Medical College of Wisconsin Program for Genomic Applications (Physgen) were designed to link chromosomes with physiological function in consomic strains derived from a cross between Dahl salt-sensitive SS/JrHsdMcwi (SS) and Brown Norway normotensive BN/NHsdMcwi (BN) rats. The specific goal of the vascular protocol was to characterize the responses of aortic rings from these strains to vasoconstrictor and vasodilator stimuli (phenylephrine, acetylcholine, sodium nitroprusside, and bath hypoxia) to identify chromosomes that either increase or decrease vascular reactivity to these vasoactive stimuli. Because previous studies demonstrated sex-specific quantitative trait loci (QTLs) related to regulation of cardiovascular phenotypes in an F2 cross between the parental strains, males and females of each consomic strain were included in all experiments. As there were significant sex-specific differences in aortic sensitivity to vasoconstrictor and vasodilator stimuli compared with the parental SS strain, we report the results of the females separately from the males. There were also sex-specific differences in aortic ring sensitivity to these vasoactive stimuli in consomic strains that were fed a high-salt diet (4% NaCl) for 3 wk to evaluate salt-induced changes in vascular reactivity. Differences in genetic architecture could contribute to sex-specific differences in the development and expression of cardiovascular diseases via differential regulation and expression of genes. Our findings are the first to link physiological traits with specific chromosomes in female SS rats and support the idea that sex is an important environmental variable that plays a role in the expression and regulation of genes.

2006 ◽  
Vol 26 (3) ◽  
pp. 218-225 ◽  
Author(s):  
Mary Pat Kunert ◽  
Ines Drenjancevic-Peric ◽  
Melinda R. Dwinell ◽  
Julian H. Lombard ◽  
Allen W. Cowley ◽  
...  

Chromosomal substitution strains afford the opportunity to discover regions of the rat genome that contain genes related to cardiovascular traits with the long-range goal of linking these genes to physiological function. PhysGen (Programs for Genomic Applications) created a consomic panel of rats derived from the introgression of a single chromosome (≥95% of the BN chromosome, one at a time) of the Brown Norway (BN/NHsdMcwi) rat onto the homogeneous genetic background of the Dahl salt-sensitive rat (SS/JrHsdMcwi). For 3 wk before the experiment, the rats were maintained on a low-salt diet (0.4% NaCl). The dose response of aortic rings from each strain of rat to phenylephrine, acetylcholine, sodium nitroprusside, and three different levels of tissue bath hypoxia (10, 5, and 0% O2) was measured and compared with the parental SS rat. To maximize the possibility that differences among the strains would become apparent, each strain of rat including the parental SS and BN was also studied after being maintained on a high-salt diet (4.0% NaCl) for 3 wk. If the response of the aortic ring from a consomic strain to these vasoactive substances was different from that of the SS parental strain, it was concluded that the introgressed chromosome contained a gene or genes that contributed to that difference. Because the BN chromosome is removed from its native background and the SS rat loses a native chromosome, it is also necessary to consider the contribution of changes in gene-to-gene interaction.


2013 ◽  
Vol 143 (9) ◽  
pp. 1406-1413 ◽  
Author(s):  
Gaurav Chugh ◽  
Mohammad Asghar ◽  
Gaurav Patki ◽  
Ritu Bohat ◽  
Faizan Jafri ◽  
...  

2007 ◽  
Vol 31 (2) ◽  
pp. 228-235 ◽  
Author(s):  
Carol Moreno ◽  
Mary L. Kaldunski ◽  
Tao Wang ◽  
Richard J. Roman ◽  
Andrew S. Greene ◽  
...  

Previous studies have indicated that substitution of chromosome 13 of the salt-resistant Brown Norway BN/SsNHsdMcwi (BN) rat into the genomic background of the Dahl salt-sensitive SS/JrHsdMcwi (SS) rat attenuates the development of salt-sensitive hypertension and renal damage. To identify the regions within chromosome 13 that attenuate the development of hypertension during a high-salt diet in the SS rat, we phenotyped a series of overlapping congenic lines covering chromosome 13, generated from an intercross between the consomic SS-13BN rat and the SS rat. Blood pressure was determined in chronically catheterized rats after 2 wk of high-salt diet (8% NaCl) together with microalbuminuria as an index of renal damage. Four discrete regions were identified, ranging in size from 4.5 to 16 Mbp, each of which independently provided significant protection from hypertension during high-salt diet, reducing blood pressure by 20–29 mmHg. Protection was more robust in female than male rats in some of the congenic strains, suggesting a sex interaction with some of the genes determining blood pressure during high-salt diet. Among the 23 congenic strains, several regions overlapped. When three of the “protective” regions were combined onto one broad congenic strain, no summation effect was seen, obtaining the same decrease in blood pressure as with each one independently. We conclude from these studies that there are four regions within chromosome 13 containing genes that interact epistatically and influence arterial pressure.


2020 ◽  
Vol 14 ◽  
pp. 117954682090284
Author(s):  
Abdullahi Adejare ◽  
Ahmed Oloyo ◽  
Chikodi Anigbogu ◽  
Smith Jaja

Background: Abnormal vascular reactivity and reduced expression of endothelial nitric oxide synthase ( eNOS) gene are hallmark of salt-induced hypertension in rats. Although l-arginine is an established vasodilator, the mechanism by which it modulates vascular reactivity in salt-induced hypertension is not clearly understood. Objectives: This study was designed to investigate the mechanism by which oral l-arginine supplementation modulates vascular reactivity and eNOS gene expression in Sprague-Dawley rats fed a high-salt diet. Methods: Forty-eight weaned male Sprague-Dawley rats of weight range 90 to 110 g were randomly divided into 6 groups of 8 rats per group. Group I was fed normal rat chow ad libitum and served as the Normal Diet group. Group II was fed a diet that contained 8% NaCl. Groups III and IV took normal and high-salt diet, respectively, and then received oral l-arginine supplementation (100 mg/kg/day), while groups V and VI took normal and high-salt diet, respectively, and then were co-administered with both l-arginine and l-nitro-arginine methyl ester (L-NAME; 100 mg/kg/day and 40 mg/kg/day, respectively) orally. At the end of 12-week experimental period, the animals were sacrificed to assess vascular reactivity and gene expression level. Results: Our results show that high-salt diet significantly reduced ( P < .05) endothelium-dependent relaxation response to acetylcholine and qualitatively reduced eNOS gene expression in the abdominal aorta of the rats. However, l-arginine supplementation improved the impaired endothelium-dependent relaxation and nitric oxide level while ameliorating the reduced eNOS gene expressions. Conclusion: This study suggests that oral supplementation of l-arginine enhances endothelial-dependent relaxation in rats fed a high-salt diet by ameliorating eNOS gene expression in the abdominal aorta of the rats.


2017 ◽  
Vol 24 (04) ◽  
pp. 580-588
Author(s):  
Kaukab Anjum ◽  
Asma Ali ◽  
Uzma Shahid

Background: Nutrition is an important determinant of bone health. Micronutrients,other than calcium has been paid less attention to-date in the prevention and treatment of bonediseases. Objective: To evaluate the protective effect of zinc on high salt induced gross changesin humerus and femur of rats. Study design: Analytical control randomized trial. Place andduration of study: Islamic International Medical College, Rawalpindi, hosted the research withthe cooperation of National Institute of Health; Islamabad. The study was approved by Ethicalreview committee of Riphah international university before its initiation. It took six months tocomplete the research (Sep 2015-March 2016). Material and methods: Forty five adult femaleSprague Dawley, 10-12 weeks old rats were used in the study. Three groups were made, eachhaving fifteen rats. Control group C (N=15) received laboratory diet without any alteration.Experimental group A (N=15) were served with high salt diet (8%NaCl) whereas experimentalgroup B (N=15) animals were given high salt diet augmented with zinc (50mg/kg/day).Allgroups were given the diet for eight weeks. Animals were weighed at the start and end ofstudy after which they were sacrificed. Left humeri and femora of all rats were obtained. Weightand mid shaft diameters of bones were recorded. The results were compiled after comparisonamongst all the groups. Results: Marked gross changes were witnessed in experimentalgroups. These changes were of greater severity in high salt diet group as compared to the zincsupplemented group in which reverse beneficial effects were noticed. After zinc administration,there was substantial increase in the weight of animals and bones with concurrent increase inmid shaft diameters. Conclusion: Zinc has a Protective role against high salt induced damageon the gross parameters of bones.


2012 ◽  
Vol 26 (S1) ◽  
Author(s):  
Ahmed Kolade Oloyo ◽  
Yakubu Momoh ◽  
Olusoga Sofola ◽  
Adebayo Oyekan

Hypertension ◽  
2017 ◽  
Vol 70 (suppl_1) ◽  
Author(s):  
Olga Berillo ◽  
Sofiane Ouerd ◽  
Ku-Geng Huo ◽  
Chantal Richer ◽  
Daniel Sinnett ◽  
...  

Background: Three congenic rat strains (SB2a, SB2b and SB2e) were created by chromosome (Chr) 2 fragment introgression from normotensive Brown Norway (BN) rats into hypertensive Dahl salt sensitive (SS) background. SB2a and SB2b rats fed a normal-salt diet presented reduced blood pressure (BP) and inflammation when compared to SS rats. We hypothesized that BN-Chr2 contains antihypertensive and anti-inflammatory genes that could prevent high-salt diet (HSD)-induced BP elevation and vascular injury in SB2a and SB2b rats. These genes will be identified using microRNA (miRNA) and total RNA expression profiling analysis in aorta of congenic rats fed a HSD. Methods and Results: Four-to-6 week-old male SS, SS, SB2a and SB2b rats were fed a HSD (4% NaCl) for 8 weeks or until they developed a stroke as manifested by seizures. Systolic blood pressure (SBP) was measured by telemetry. Systolic BP was higher in SB2b but not SB2a when compared to SS (185±8, 167±7 vs 168±5 mm Hg). Total RNA was extracted from aorta and used to construct libraries for small and total RNA sequencing using Illumina HiSeq-2500. The bioinformatics pipeline included: FastQC for quality control, STAR for genome (Rattus norvegicus, release-86) alignment, mirdeep2 for miRNA annotation and counting, Htseq-count for mRNA and long non-coding RNA annotation and counting; R for differential expression analysis. Differentially expressed miRNAs and genes (mRNAs and non-coding RNAs) were identified in SB2a vs SS (miRNAs: 11 up and 10 down; genes: 92 up and 91 down) and in SB2b vs SS (miRNAs: 3 up and 2 down; genes: 10 up and 13 down) with FDR<0.05. Differentially expressed genes encoded within different BN-Chr2 congenic portions were identified in SB2a vs SS (genes: 7 up and 2 down) and SB2b vs SS (genes: 6 up and 4 down). Conclusions and Perspectives: Differentially expressed BN-Chr2 encoded genes were identified in aorta of congenic SB2a and SB2b rats fed HSD. Whether these genes play a role in HSD-induced BP elevation and vascular inflammation remains to be determined.


Hypertension ◽  
2001 ◽  
Vol 38 (3) ◽  
pp. 730-735 ◽  
Author(s):  
Laura A. Barron ◽  
Jena B. Giardina ◽  
Joey P. Granger ◽  
Raouf A. Khalil

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Osama A. A. Ahmed ◽  
Ahmad S. Azhar ◽  
Mayada M. Tarkhan ◽  
Khadijah S. Balamash ◽  
Hany M. El-Bassossy

Multiple risk factors combine to increase the risk of vascular dysfunction in patients suffering from metabolic syndrome (MetS). The current study investigates the extent to which quercetin (Q) and chrysin (CH) protect against vascular dysfunction in MetS rats. MetS was induced by feeding rats a high-salt diet (3%) and fructose-enriched water (10%) for 12 weeks. Thoracic aorta was isolated from MetS rats and from control rats, with the latter being injured by methylglyoxal (MG). Aortae were incubated with CH and Q, and vascular reactivity was evaluated through the analysis of aortic contraction and relaxation in response to PE and ACh, respectively. The formation of advanced glycation end products (AGEs) and the free radical scavenging activity of 1,1-diphenyl-2-picrylhydrazyl (DPPH) were also evaluated following the introduction of CH and Q. The increased vasoconstriction and impaired vasodilation in MetS aortae were significantly ameliorated by Q and CH. Similarly, they ameliorated glycation-associated exaggerated vasoconstriction and impaired vasodilation produced by MG in control aortae. In addition, both Q and CH were effective in reducing the formation of AGEs and inhibition of glycosylation in response to MG or fructose treatment. Finally, Q successfully scavenged DPPH free radicals while CH showed significant vasodilation of precontracted aorta that was inhibited by L-NAME. In conclusion, Q and CH provide protection against vascular dysfunction in MetS by interfering with AGEs formations and AGEs-associated vascular deterioration, with CH being largely dependent on NO-mediated mechanisms of vasodilation.


2019 ◽  
Vol 20 (20) ◽  
pp. 5188 ◽  
Author(s):  
Nataša Kozina ◽  
Zrinka Mihaljević ◽  
Mirela Baus Lončar ◽  
Martina Mihalj ◽  
Mihael Mišir ◽  
...  

High salt (HS) dietary intake leads to impaired vascular endothelium-dependent responses to various physiological stimuli, some of which are mediated by arachidonic acid (AA) metabolites. Transgenic Tff3−/− gene knockout mice (Tff3−/−/C57BL/6N) have changes in lipid metabolism which may affect vascular function and outcomes of stroke. We aimed to study the effects of one week of HS diet (4% NaCl) on vascular function and stroke induced by transient occlusion of middle cerebral artery in Tff3−/− and wild type (WT/C57BL/6N) mice. Flow-induced dilation (FID) of carotid artery was reduced in WT-HS mice, but not affected in Tff3−/−-HS mice. Nitric oxide (NO) mediated FID. NO production was decreased with HS diet. On the contrary, acetylcholine-induced dilation was significantly decreased in Tff3−/− mice on both diets and WT-HS mice. HS intake and Tff3 gene depletion affected the structural components of the vessels. Proteomic analysis revealed a significant effect of Tff3 gene deficiency on HS diet-induced changes in neuronal structural proteins and acute innate immune response proteins’ expression and Tff3 depletion, but HS diet did not increase the stroke volume, which is related to proteome modification and upregulation of genes involved mainly in cellular antioxidative defense. In conclusion, Tff3 depletion seems to partially impair vascular function and worsen the outcomes of stroke, which is moderately affected by HS diet.


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