Introduction
The Gut Epithelium Barrier
Permeability of the Gut Barrier
The Paracellular Pathway
Measuring Intestinal Permeability
Ex vivo Measurement
In vivo Measurements
Dual and Multisugar Tests
Blood Biomarkers of Intestinal Permeability
Gut Permeability and Hypertension
Study Ref | Animal Model of Hypertension | Comparison Animal Model | Measure of gut permeability | Other relevant measurements |
---|---|---|---|---|
SHR rat: | ||||
Santisteban et al. 2017 [92] | Pre-hypertensive 4-week-old SHRs | 4-week-old WKY rats | ND: FITC-Dextran Protein expression (WB) SI: ↓ ZO-1, claudin-4, cingulin. ND: occludin Colon: ↓ occludin, ZO-1, claudin-4, cingulin | |
Santisteban et al. 2017 [92] | 20-week-old SHRs | 20-week-old WKY rats | ↑ FITC-Dextran Protein expression (WB) SI: ↓ occludin, ZO-1, claudin-4. ND: cingulin Colon:↓ occludin, ZO-1, cingulin. ND: Claudin-4 | ↓ goblet cells in small intestine ↑ Fibrotic area in small intestine ↓ intestinal blood perfusion |
Jaworska et al. 2017 [93] | 24–26-week-old SHRs | 24–26 week old WKY rats | ↑ portal vein TMA following intracolonic TMA infusion Protein expression (IF): ND: colonic occludin or ZO-1 | ↓ intestinal blood flow |
Wang et al. 2021 [94] | Pre-hypertensive 5-week-old SHRs | 5-week-old WKY rats | Colon Ussing Chamber ↑ paracellular permeability, ND: transcellular permeability Protein expression (WB) Colon: ↓ claudin5, occludin, ZO-1 | |
Ang II infusion model: | ||||
Santisteban et al. 2017 [92] | 8-week-old Sprague Dawley Rats infused with Ang II | 8-week-old Sprague Dawley Rats infused with saline | ↑ FITC-Dextran Protein expression (WB) SI: ↓ occludin, ZO-1, cingulin. ND: claudin-4 Colon: ↓ occludin, ZO-1, cingulin, claudin-4 | |
Kim et al. 2018 [48] | C57BL/6 mice infused with Ang II (4-weeks) | C57BL/6 mouse infused with saline | ↑ FITC-Dextran Gene expression:↓ occludin, ZO-1. ND: claudin-4 | |
Kaye et al. 2020 [96] | C57BL/6 J mice infused with Ang II (4-weeks) | C57BL/6 J mouse infused with saline | Gene expression: ↓ ZO-1 | ↑ TNF-α and IL-6 intestinal gene expression |
DOCA salt model: | ||||
Robles-Vera 2020 [97] | Male Wistar rats DOCA-salt induced hypertension | Male Wistar rats | ↑ plasma LPS Gene expression: ↓ occludin and ZO-1 | Gene expression: ↓ mucin-2 and mucin-3 |
Evidence from Experimental Animal Models of Hypertension
Evidence from Human and Non-Human Primates
Study Ref | Study Type | Hypertensive Cohort | Control Cohort | Measure of gut permeability |
---|---|---|---|---|
Kim et al. 2018 [48] | Cross-sectional | SBP ≥ 140 mm Hg irrespective of participant’s antihypertensive drug regimen (n = 18) | SBP ≤ 130 mm Hg irrespective of participant’s antihypertensive drug regimen (n = 17) | ↑ plasma I-FAPB ↑ plasma LPS ↑ plasma Zonulin |
Ntlahla et al. 2021 [98] | Cross-sectional | SBP ≥ 140 mmHg and/or DBP ≥ 90 mmHg (n = 27) | SBP ≤ 120 mm Hg and DBP ≤ 80 mm Hg (n = 69) | ↑ plasma Zonulin |
Li et al. 2021 [99] | Retrospective Inpatient Records | SBP ≥ 140 mm Hg and/or DBP ≥ 90 mm Hg irrespective of participant’s antihypertensive drug regimen (n = 106) | SBP ≤ 130 mm Hg and DPB ≤ 80 mm Hg irrespective of participant’s antihypertensive drug regimen (n = 251) | ↑ % with elevated DAO, ↑ % with elevated LPS, ND D-lactate |
Pregnancy: | ||||
Tomsett et al. 2020 [100] | Prospective Case–Control | Women who developed hypertension in late pregnancy (n = 19) | Women who remain normotensive during pregnancy (n = 36) | ↑ plasma Zonulin at 28 weeks gestation ND plasma Zonulin at 16 weeks gestation |
Wang et al. 2006 [101] | Cross-sectional | Pregnant women with pre-eclampsia (n = 13) | Women who remain normotensive during pregnancy (n = 13) | ↑ plasma LPB at parturition |
Mutluoglu et al. 2023 [102] | Cross-sectional | Pregnant women with pre-eclampsia (n = 22) | Pregnant women without pre-eclampsia (n = 22) | ↓ plasma LBP and ↓ plasma Zonulin between 22–40 weeks of gestation |
Non-Human Primates: | ||||
Vemuri et al. 2022 [103•] | Cross-sectional | Vervet monkeys (n = 153) | LBP positively correlated with SBP and DBP | |
Vemuri et al. 2022 [103•] | Longitudinal | Adult male rhesus monkeys with SBP ≥ 120 mm Hg and/or DBP ≥ 80 mm Hg (n = 8) | Adult male rhesus monkeys with SBP ≤ 120 mm Hg and/or DBP ≤ 80 mm Hg (n = 8) | ↑ plasma LBP at baseline and month 6, 18 and 27 |