Plasma ET-1 Concentrations are Elevated in Patients with Hypertension – Meta-Analysis of Clinical Studies

Abstract

Background/Aims: A recent study revealed that global overexpression of ET-1 causes a slight reduction in systemic blood pressure. Moreover, heterozygous ET-1 knockout mice are hypertensive. The role of ET-1 in human hypertension was so far not addressed by a strict meta-analysis of published human clinical studies. Methods: We included studies published between January 1, 1990 and February 28, 2017. We included case control studies analyzing untreated essential hypertension or hypertensive patients where antihypertensive medication was discontinued for at least two weeks. Based on the principle of Cochrane systematic reviews, case control studies (CCSs) in PubMed (Medline) and Google Scholar designed to identify the role of endothelin-1 (ET-1) in the pathophysiological of hypertension were screened. Review Manager Version 5.0 (Rev-Man 5.0) was applied for statistical analysis. Mean difference and 95% confidence interval (CI) were shown in inverse variance (IV) fixed-effects model or IV random-effects models. Results: Eleven studies fulfilling our in- and exclusion criteria were eligible for this meta-analysis. These studies included 450 hypertensive patients and 328 controls. Our meta-analysis revealed that ET-1 plasma concentrations were higher in hypertensive patients as compared to the control patients [mean difference between groups 1.57 pg/mL, 95%CI [0.47∼2.68, P = 0.005]. These finding were driven by patients having systolic blood pressure higher than 160 mmHg and diastolic blood pressure higher than 100 mmHg. Conclusions: This meta-analysis showed that hypertensive patients do have elevated plasma ET-1 concentrations. This finding is driven by those patients with high systolic/diastolic blood pressure. Given that the ET-1 gene did not appear in any of the whole genome association studies searching for hypertension associated gene loci, it is very likely that the elevated plasma ET-1 concentrations in hypertensive patients are secondary to hypertension and may reflect endothelial cell damage.

Plasma ET-1 Concentrations Are Elevated in Pregnant Women with Hypertension -Meta-Analysis of Clinical Studies

“…In particular women with preeclampsia (hypertensive pregnant women with proteinuria) have substantially elevated plasma ET-1 concentration as compared to pregnant women with normal blood pressure. Comparing the current study results with a recent meta-analysis in non-pregnant hypertensive patients [12], it became obvious that the ET-1 elevation is much more pronounced in hypertensive pregnant women as compared to hypertensive non-pregnant patients. Our data might suggest that ET-1 play a causal role in humans in the pathogenesis of pregnancy related hypertensive diseases.…”

“…This meta-analysis provides robust evidence that systemic ET-1 overexpression in mice lowers blood pressure in an age-dependent manner [11]. A subsequent meta-analysis -on the other hand -revealed that ET-1 plasma concentrations are elevated in humans with essential hypertension [12]. Given these contradictory findings in transgenic endothelin rodent models and humans with essential hypertension as well as the initial hypothesis that ET-1 might be involved in the pathogenesis of hypertension during pregnancy, the aim of the current study therefore was to perform a systematic review and meta-analysis of all so far published studies reporting ET-1 plasma concentrations in pregnant women.…”

“…The meta-analysis was conducted according to principles and methods that we recently published [11,12,20,21].…”

Endothelin-1 Level in Patients with Simple Renal Cyst

“…6 The authors reported that plasma ET-1 levels were higher by 42% in hypertensive patients than in control patients. 15 The effect of endothelin-1 on blood pressure occurs via tubular water and salt excretion, constriction of smooth muscle cells, modulating sympathetic nerve activity and vasodilatation with nitric oxide. The articles about ET-1 are about autosomal dominant PKD in the literature.…”

Association of endothelin-1 with oxidative stress and inflammatory response in pre-hypertensives

“…11 Saito et al have documented the relationship between ET-1 levels and essential hypertension suggesting the causative role for ET-1 in the pathogenesis of the disease. 12,13 But the association between endothelial dysfunction, oxidation stress and systemic infl ammation in the development of pre-hypertension remains clear. Hence the present study was designed to investigate the association of endothelin-1 with oxidative stress and infl ammatory response in pre-hypertensives.…”