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Article ; Online: Microbiota-associated mechanisms underlying sexual dimorphism in hypertension.

Dasinger, John Henry / Joe, Bina / Abais-Battad, Justine M

Microbiota and host

2023 Volume 1, Issue 1

Abstract: Consistent research over the last 20 years has shown that there are clear sex differences in the pathogenesis of hypertension, the leading risk factor for the development of cardiovascular diseases. More recently, there is evidence in both humans and ... ...

Abstract	Consistent research over the last 20 years has shown that there are clear sex differences in the pathogenesis of hypertension, the leading risk factor for the development of cardiovascular diseases. More recently, there is evidence in both humans and experimental animal models that causally implicates the gut microbiota in hypertension. It therefore follows that sex differences in the gut microbiota may mediate the extent of disease between sexes. This new field is rapidly changing and advancing, and the purpose of this review is to cover the most up-to-date evidence regarding the sexual dimorphism of the gut microbiota and its potential influence on the differential manifestation of hypertension in males versus females. Emphasis will be placed on the mechanisms thought to contribute to these sex differences in both the gut microbiota and hypertension, including sex steroid hormones, gut-derived metabolites, the immune system, and pregnancy.
Language	English
Publishing date	2023-11-23
Publishing country	England
Document type	Journal Article
ISSN	2753-6955
ISSN (online)	2753-6955
DOI	10.1530/mah-23-0016
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Article ; Online: Dietary Protein, Chronic Salt-Sensitive Hypertension, and Kidney Damage.

Mattson, David L / Dasinger, John Henry / Abais-Battad, Justine M

Kidney360

2023 Volume 4, Issue 8, Page(s) 1181–1187

Abstract: It has been estimated that over a fifth of deaths worldwide can be attributed to dietary risk factors. A particularly serious condition is salt-sensitive (SS) hypertension and renal damage, participants of which demonstrate increased morbidity and ... ...

Abstract	It has been estimated that over a fifth of deaths worldwide can be attributed to dietary risk factors. A particularly serious condition is salt-sensitive (SS) hypertension and renal damage, participants of which demonstrate increased morbidity and mortality. Notably, a large amount of evidence from humans and animals has demonstrated that other components of the diet can also modulate hypertension and associated end-organ damage. Evidence presented in this review provides support for the view that immunity and inflammation serve to amplify the development of SS hypertension and leads to malignant disease accompanied by tissue damage. Interestingly, SS hypertension is modulated by changes in dietary protein intake, which also influences immune mechanisms. Together, the evidence presented in this review from animal and human studies indicates that changes in dietary protein source have profound effects on the gut microbiota, microbiota-derived metabolites, gene expression, immune cell activation, the production of cytokines and other factors, and the development of SS hypertension and kidney damage.
MeSH term(s)	Animals ; Humans ; Dietary Proteins/adverse effects ; Dietary Proteins/metabolism ; Blood Pressure/physiology ; Kidney Diseases/etiology ; Hypertension/etiology ; Kidney/metabolism ; Sodium Chloride, Dietary/adverse effects ; Sodium Chloride, Dietary/metabolism
Chemical Substances	Dietary Proteins ; Sodium Chloride, Dietary
Language	English
Publishing date	2023-07-10
Publishing country	United States
Document type	Review ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	2641-7650
ISSN (online)	2641-7650
DOI	10.34067/KID.0000000000000210
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Article ; Online: Gut-Immune-Kidney Axis: Influence of Dietary Protein in Salt-Sensitive Hypertension.

Mattson, David L / Dasinger, John Henry / Abais-Battad, Justine M

Hypertension (Dallas, Tex. : 1979)

2022 Volume 79, Issue 11, Page(s) 2397–2408

Abstract: Humans with salt-sensitive hypertension demonstrate increased morbidity, increased mortality, and renal end-organ damage when compared with normotensive subjects or those with salt-resistant hypertension. Substantial evidence from humans and animals has ... ...

Abstract	Humans with salt-sensitive hypertension demonstrate increased morbidity, increased mortality, and renal end-organ damage when compared with normotensive subjects or those with salt-resistant hypertension. Substantial evidence from humans and animals has also demonstrated the role of dietary components other than salt to modulate hypertension. Evidence presented in this review provides support for the view that immunity and inflammation serve to amplify the development of salt-sensitive hypertension and leads to malignant disease accompanied by end-organ damage. Interestingly, salt-sensitive disease is modulated by changes in dietary protein intake, which also influences immune mechanisms. Together, the evidence presented in this review from animal and human studies indicates that changes in dietary protein source have profound effects on the gut microbiota, microbiota-derived metabolites, DNA methylation, gene expression, immune cell activation, the production of cytokines and other factors, and the development of salt-sensitive hypertension and related disease phenotypes.
MeSH term(s)	Rats ; Animals ; Humans ; Rats, Inbred Dahl ; Dietary Proteins ; Sodium Chloride, Dietary/adverse effects ; Sodium Chloride, Dietary/metabolism ; Hypertension/metabolism ; Kidney/metabolism ; Blood Pressure/physiology
Chemical Substances	Dietary Proteins ; Sodium Chloride, Dietary
Language	English
Publishing date	2022-08-19
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	423736-5
ISSN	1524-4563 ; 0194-911X ; 0362-4323
ISSN (online)	1524-4563
ISSN	0194-911X ; 0362-4323
DOI	10.1161/HYPERTENSIONAHA.122.18556
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Article ; Online: Functional NADPH oxidase 2 in T cells amplifies salt-sensitive hypertension and associated renal damage.

Walton, Samuel D / Dasinger, John Henry / Burns, Emily C / Cherian-Shaw, Mary / Abais-Battad, Justine M / Mattson, David L

American journal of physiology. Renal physiology

2023 Volume 325, Issue 2, Page(s) F214–F223

Abstract: Infiltrating T cells in the kidney amplify salt-sensitive (SS) hypertension and renal damage, but the mechanisms are not known. Genetic deletion of T cells ( ... ...

Abstract	Infiltrating T cells in the kidney amplify salt-sensitive (SS) hypertension and renal damage, but the mechanisms are not known. Genetic deletion of T cells (SS
MeSH term(s)	Rats ; Animals ; Sodium Chloride ; Albuminuria ; NADPH Oxidase 2/genetics ; Reactive Oxygen Species ; T-Lymphocytes ; Rats, Inbred Dahl ; Kidney ; Hypertension/genetics ; Sodium Chloride, Dietary ; NADPH Oxidases/genetics
Chemical Substances	Sodium Chloride (451W47IQ8X) ; NADPH Oxidase 2 (EC 1.6.3.-) ; Reactive Oxygen Species ; Sodium Chloride, Dietary ; NADPH Oxidases (EC 1.6.3.-)
Language	English
Publishing date	2023-06-15
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	603837-2
ISSN	1522-1466 ; 0363-6127
ISSN (online)	1522-1466
ISSN	0363-6127
DOI	10.1152/ajprenal.00014.2023
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Article ; Online: Amplification of Salt-Sensitive Hypertension and Kidney Damage by Immune Mechanisms.

Mattson, David L / Dasinger, John Henry / Abais-Battad, Justine M

American journal of hypertension

2020 Volume 34, Issue 1, Page(s) 3–14

Abstract: Humans with salt-sensitive (SS) hypertension demonstrate increased morbidity, increased mortality, and renal end-organ damage when compared with normotensive subjects or those with salt-resistant hypertension. Increasing evidence indicates that immune ... ...

Abstract	Humans with salt-sensitive (SS) hypertension demonstrate increased morbidity, increased mortality, and renal end-organ damage when compared with normotensive subjects or those with salt-resistant hypertension. Increasing evidence indicates that immune mechanisms play an important role in the full development of SS hypertension and associated renal damage. Recent experimental advances and studies in animal models have permitted a greater understanding of the mechanisms of activation and action of immunity in this disease process. Evidence favors a role of both innate and adaptive immune mechanisms that are triggered by initial, immune-independent alterations in blood pressure, sympathetic activity, or tissue damage. Activation of immunity, which can be enhanced by a high-salt intake or by alterations in other components of the diet, leads to the release of cytokines, free radicals, or other factors that amplify renal damage and hypertension and mediate malignant disease.
MeSH term(s)	Blood Pressure/physiology ; Humans ; Hypertension/complications ; Hypertension/immunology ; Hypertension/physiopathology ; Immunity ; Kidney Diseases/etiology ; Kidney Diseases/immunology ; Sodium Chloride, Dietary/adverse effects
Chemical Substances	Sodium Chloride, Dietary
Language	English
Publishing date	2020-07-24
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	639383-4
ISSN	1941-7225 ; 1879-1905 ; 0895-7061
ISSN (online)	1941-7225 ; 1879-1905
ISSN	0895-7061
DOI	10.1093/ajh/hpaa124
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Zs.A 2329: Show issues

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Article ; Online: Dietary Protein: Mechanisms Influencing Hypertension and Renal Disease.

Dasinger, John Henry / Fehrenbach, Daniel J / Abais-Battad, Justine M

Current hypertension reports

2020 Volume 22, Issue 2, Page(s) 13

Abstract: Purpose of review: This review will provide an in-depth coverage of the epidemiological and pre-clinical literature surrounding the role of dietary protein in hypertension, with a special emphasis on the history of our work on the Dahl salt-sensitive ... ...

Abstract	Purpose of review: This review will provide an in-depth coverage of the epidemiological and pre-clinical literature surrounding the role of dietary protein in hypertension, with a special emphasis on the history of our work on the Dahl salt-sensitive rat. Recent findings: Our studies have dedicated much effort into understanding the relationship between dietary protein and its effect on the development of salt-sensitive hypertension and renal injury. Our evidence over the last 15 years have demonstrated that both the source and amount of dietary protein can influence the severity of disease, where we have determined mechanisms related to immunity, the maternal environment during pregnancy, and more recently the gut microbiota, which significantly contribute to these diet-induced effects. Deeper understanding of these dietary protein-related mechanisms may provide insight on the plausibility of dietary modifications as future therapeutic avenues for hypertension and renal disease.
MeSH term(s)	Animals ; Blood Pressure ; Dietary Proteins ; Female ; Humans ; Hypertension ; Kidney ; Kidney Diseases ; Pregnancy ; Rats ; Rats, Inbred Dahl ; Sodium Chloride, Dietary
Chemical Substances	Dietary Proteins ; Sodium Chloride, Dietary
Language	English
Publishing date	2020-02-03
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2057367-4
ISSN	1534-3111 ; 1522-6417
ISSN (online)	1534-3111
ISSN	1522-6417
DOI	10.1007/s11906-020-1018-8
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Zs.A 5522: Show issues

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Article ; Online: Influences of environmental factors during preeclampsia.

Dasinger, John Henry / Abais-Battad, Justine M / Mattson, David L

American journal of physiology. Regulatory, integrative and comparative physiology

2020 Volume 319, Issue 1, Page(s) R26–R32

Abstract: Preeclampsia is a pregnancy-specific disorder that impacts 5-8% of pregnancies and has long-term cardiovascular and metabolic implications for both mother and fetus. The mechanisms are unclear; however, it is believed that preeclampsia is characterized ... ...

Abstract	Preeclampsia is a pregnancy-specific disorder that impacts 5-8% of pregnancies and has long-term cardiovascular and metabolic implications for both mother and fetus. The mechanisms are unclear; however, it is believed that preeclampsia is characterized by abnormal vascularization during placentation resulting in the manifestation of clinical signs such as hypertension, proteinuria, and endothelial dysfunction. Although there is no current cure to alleviate the clinical signs, an emerging area of interest in the field is the influence of environmental factors including diet on the risk of preeclampsia. Because preeclampsia has serious cardiovascular implications to both the mother and fetus and most antihypertensive medications are contraindicated in pregnancy, it is important to investigate other potential therapeutic options such as dietary manipulation. The emerging field of nutrigenomics links diet with the gene expression of known pathways such as oxidative stress and inflammation via microbiome-mediated metabolites and could serve as one potential avenue of therapeutic targets for preeclampsia. Although the exact role of nutrition in the pathogenesis of preeclampsia is unknown, this review will focus on known pathways involved in the development of preeclampsia and how dietary intake modulates the microbiome, oxidative stress, and inflammation with an emphasis on nutrigenomics as a potential avenue of further investigation to better understand this pathology.
MeSH term(s)	Adult ; Diet ; Environment ; Female ; Humans ; Microbiota ; Nutrigenomics ; Pre-Eclampsia/genetics ; Pre-Eclampsia/metabolism ; Pregnancy
Language	English
Publishing date	2020-05-20
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	603839-6
ISSN	1522-1490 ; 0363-6119
ISSN (online)	1522-1490
ISSN	0363-6119
DOI	10.1152/ajpregu.00020.2020
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Article ; Online: Gender differences in developmental programming of cardiovascular diseases.

Dasinger, John Henry / Alexander, Barbara T

Clinical science (London, England : 1979)

2016 Volume 130, Issue 5, Page(s) 337–348

Abstract: Hypertension is a risk factor for cardiovascular disease, the leading cause of death worldwide. Although multiple factors contribute to the pathogenesis of hypertension, studies by Dr David Barker reporting an inverse relationship between birth weight ... ...

Abstract	Hypertension is a risk factor for cardiovascular disease, the leading cause of death worldwide. Although multiple factors contribute to the pathogenesis of hypertension, studies by Dr David Barker reporting an inverse relationship between birth weight and blood pressure led to the hypothesis that slow growth during fetal life increased blood pressure and the risk for cardiovascular disease in later life. It is now recognized that growth during infancy and childhood, in addition to exposure to adverse influences during fetal life, contributes to the developmental programming of increased cardiovascular risk. Numerous epidemiological studies support the link between influences during early life and later cardiovascular health; experimental models provide proof of principle and indicate that numerous mechanisms contribute to the developmental origins of chronic disease. Sex has an impact on the severity of cardiovascular risk in experimental models of developmental insult. Yet, few studies examine the influence of sex on blood pressure and cardiovascular health in low-birth weight men and women. Fewer still assess the impact of ageing on sex differences in programmed cardiovascular risk. Thus, the aim of the present review is to highlight current data about sex differences in the developmental programming of blood pressure and cardiovascular disease.
MeSH term(s)	Birth Weight/physiology ; Blood Pressure/physiology ; Female ; Fetal Development/physiology ; Humans ; Hypertension/embryology ; Hypertension/etiology ; Hypertension/physiopathology ; Infant, Low Birth Weight ; Infant, Newborn ; Male ; Pregnancy ; Prenatal Exposure Delayed Effects/physiopathology ; Risk Factors ; Sex Characteristics
Language	English
Publishing date	2016-03
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	206835-7
ISSN	1470-8736 ; 0301-0538 ; 0009-0360 ; 0143-5221
ISSN (online)	1470-8736
ISSN	0301-0538 ; 0009-0360 ; 0143-5221
DOI	10.1042/CS20150611
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Article ; Online: Impact of bedding on Dahl salt-sensitive hypertension and renal damage.

Dasinger, John Henry / Walton, Samuel D / Burns, Emily C / Cherian-Shaw, Mary / Abais-Battad, Justine M / Mattson, David L

American journal of physiology. Renal physiology

2022 Volume 323, Issue 6, Page(s) F666–F672

Abstract: Salt-sensitive hypertension, increases in blood pressure in response to increased salt intake, is associated with an increased risk of morbidity, mortality, and end-organ damage compared with salt-resistant hypertension. The Dahl salt-sensitive (SS) rat ... ...

Abstract	Salt-sensitive hypertension, increases in blood pressure in response to increased salt intake, is associated with an increased risk of morbidity, mortality, and end-organ damage compared with salt-resistant hypertension. The Dahl salt-sensitive (SS) rat mimics the phenotypic characteristics observed in human hypertension when rats are challenged with a high-salt diet. Our previous work demonstrated that environmental factors, such as dietary protein, alter the severity of salt sensitivity in Dahl SS rats and should be an important consideration in experimental design. The present study investigated how the bedding on which animals were maintained (wood vs. corncob) could impact the SS phenotype in the Dahl SS rat. Animals that were maintained on corncob bedding exhibited a significant attenuation in blood pressure and renal end-organ damage in response to a high-salt diet compared with animals maintained on wood bedding. This attenuation was associated with an improvement in renal function and reduction in immune cell infiltration into the kidneys of Dahl SS rats maintained on corncob bedding. These results indicate that the type of bedding impacts the SS phenotype in the Dahl SS rat and that the bedding used in experiments can be a confounding factor to consider during data interpretation and experimental design.
MeSH term(s)	Humans ; Rats ; Animals ; Sodium Chloride, Dietary/metabolism ; Rats, Inbred Dahl ; Hypertension ; Kidney/metabolism ; Blood Pressure ; Bedding and Linens/adverse effects
Chemical Substances	Sodium Chloride, Dietary
Language	English
Publishing date	2022-09-15
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	603837-2
ISSN	1522-1466 ; 0363-6127
ISSN (online)	1522-1466
ISSN	0363-6127
DOI	10.1152/ajprenal.00201.2022
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Article ; Online: Splenocyte transfer exacerbates salt-sensitive hypertension in rats.

Fehrenbach, Daniel J / Dasinger, John Henry / Lund, Hayley / Zemaj, Jeylan / Mattson, David L

Experimental physiology

2020 Volume 105, Issue 5, Page(s) 864–875

Abstract: New findings: What is the central question of this study? Recruitment of immune cells to the kidney potentiates hypertensive pathology, but more refined methods are needed to assess these cells functionally. Adoptive transfer studies of immune cells ... ...

Abstract	New findings: What is the central question of this study? Recruitment of immune cells to the kidney potentiates hypertensive pathology, but more refined methods are needed to assess these cells functionally. Adoptive transfer studies of immune cells have been limited in rat models and especially in the study of salt-sensitive hypertension. We tested the hypothesis that splenocyte transfer into T-cell-deficient rats is sufficient to exacerbate salt-sensitive hypertension. What is the main finding and its importance? We demonstrate that transfer of splenocytes into T-cell-deficient animals exacerbates salt-sensitive hypertension, and an enrichment in the CD4 Abstract: Increasing evidence of immune system activation during the progression of hypertension and renal injury has led to a need for new methods to study individual cell types. Transfer of immune cells serves as a powerful tool to isolate effects of specific subsets. Transfer studies in Rag1
MeSH term(s)	Animals ; Blood Pressure ; Cell Transplantation/adverse effects ; Disease Models, Animal ; Disease Progression ; Hypertension/pathology ; Kidney Diseases/physiopathology ; Male ; Rats ; Rats, Inbred Dahl ; Sodium Chloride, Dietary/adverse effects ; Spleen/cytology ; Spleen/transplantation ; T-Lymphocytes
Chemical Substances	Sodium Chloride, Dietary
Language	English
Publishing date	2020-03-17
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1016295-1
ISSN	1469-445X ; 0958-0670
ISSN (online)	1469-445X
ISSN	0958-0670
DOI	10.1113/EP088340
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