Cargando…
Plasma levels of the cardiovascular protective endogenous nucleoside adenosine are reduced in patients with primary aldosteronism without affecting ischaemia‐reperfusion injury: A prospective case‐control study
BACKGROUND: Patients with primary aldosteronism (PA) experience more cardiovascular events compared to patients with essential hypertension (EHT), independent from blood pressure levels. In animals, mineralocorticoid receptor antagonists limit ischaemia‐reperfusion (IR) injury by increasing extracel...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6900001/ https://www.ncbi.nlm.nih.gov/pubmed/31659743 http://dx.doi.org/10.1111/eci.13180 |
_version_ | 1783477257749135360 |
---|---|
author | van den Berg, T. N. A. (Daniëlle) Thijssen, Dick H. J. van Mil, Anke C. C. M. van den Broek, Petra H. Rongen, Gerard A. Monajemi, Houshang Deinum, Jaap Riksen, Niels P. |
author_facet | van den Berg, T. N. A. (Daniëlle) Thijssen, Dick H. J. van Mil, Anke C. C. M. van den Broek, Petra H. Rongen, Gerard A. Monajemi, Houshang Deinum, Jaap Riksen, Niels P. |
author_sort | van den Berg, T. N. A. (Daniëlle) |
collection | PubMed |
description | BACKGROUND: Patients with primary aldosteronism (PA) experience more cardiovascular events compared to patients with essential hypertension (EHT), independent from blood pressure levels. In animals, mineralocorticoid receptor antagonists limit ischaemia‐reperfusion (IR) injury by increasing extracellular adenosine formation and adenosine receptor stimulation. Adenosine is an endogenous compound with profound cardiovascular protective effects. Firstly, we hypothesized that patients with PA have lower circulating adenosine levels which might contribute to the observed increased cardiovascular risk. Secondly, we hypothesized that by this mechanism, patients with PA are more susceptible to IR compared to patients with EHT. DESIGN: In our prospective study in 20 patients with PA and 20 patients with EHT, circulating adenosine was measured using a pharmacological blocker solution that halts adenosine metabolism after blood drawing. Brachial artery flow‐mediated dilation (FMD) before and after forearm IR was used as a well‐established method to study IR injury. RESULTS: Patients with PA had a 33% lower adenosine level compared to patients with EHT (15.3 [13.3‐20.4] vs 22.7 [19.4‐36.8] nmol/L, respectively, P < .01). The reduction in FMD after IR, however, did not differ between patients with PA and patients with EHT (−1.0 ± 2.9% vs −1.6 ± 1.6%, respectively, P = .52). CONCLUSIONS: As adenosine receptor stimulation induces various powerful protective cardiovascular effects, its lower concentration in patients with PA might be an important novel mechanism that contributes to their increased cardiovascular risk. We suggest that modulation of the adenosine metabolism is an exciting novel pharmacological opportunity to limit cardiovascular risk in patients with PA that needs further exploration. |
format | Online Article Text |
id | pubmed-6900001 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-69000012019-12-20 Plasma levels of the cardiovascular protective endogenous nucleoside adenosine are reduced in patients with primary aldosteronism without affecting ischaemia‐reperfusion injury: A prospective case‐control study van den Berg, T. N. A. (Daniëlle) Thijssen, Dick H. J. van Mil, Anke C. C. M. van den Broek, Petra H. Rongen, Gerard A. Monajemi, Houshang Deinum, Jaap Riksen, Niels P. Eur J Clin Invest Original Paper BACKGROUND: Patients with primary aldosteronism (PA) experience more cardiovascular events compared to patients with essential hypertension (EHT), independent from blood pressure levels. In animals, mineralocorticoid receptor antagonists limit ischaemia‐reperfusion (IR) injury by increasing extracellular adenosine formation and adenosine receptor stimulation. Adenosine is an endogenous compound with profound cardiovascular protective effects. Firstly, we hypothesized that patients with PA have lower circulating adenosine levels which might contribute to the observed increased cardiovascular risk. Secondly, we hypothesized that by this mechanism, patients with PA are more susceptible to IR compared to patients with EHT. DESIGN: In our prospective study in 20 patients with PA and 20 patients with EHT, circulating adenosine was measured using a pharmacological blocker solution that halts adenosine metabolism after blood drawing. Brachial artery flow‐mediated dilation (FMD) before and after forearm IR was used as a well‐established method to study IR injury. RESULTS: Patients with PA had a 33% lower adenosine level compared to patients with EHT (15.3 [13.3‐20.4] vs 22.7 [19.4‐36.8] nmol/L, respectively, P < .01). The reduction in FMD after IR, however, did not differ between patients with PA and patients with EHT (−1.0 ± 2.9% vs −1.6 ± 1.6%, respectively, P = .52). CONCLUSIONS: As adenosine receptor stimulation induces various powerful protective cardiovascular effects, its lower concentration in patients with PA might be an important novel mechanism that contributes to their increased cardiovascular risk. We suggest that modulation of the adenosine metabolism is an exciting novel pharmacological opportunity to limit cardiovascular risk in patients with PA that needs further exploration. John Wiley and Sons Inc. 2019-11-25 2019-12 /pmc/articles/PMC6900001/ /pubmed/31659743 http://dx.doi.org/10.1111/eci.13180 Text en © 2019 The Authors. European Journal of Clinical Investigation published by John Wiley & Sons Ltd on behalf of Stichting European Society for Clinical Investigation Journal Foundation This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
spellingShingle | Original Paper van den Berg, T. N. A. (Daniëlle) Thijssen, Dick H. J. van Mil, Anke C. C. M. van den Broek, Petra H. Rongen, Gerard A. Monajemi, Houshang Deinum, Jaap Riksen, Niels P. Plasma levels of the cardiovascular protective endogenous nucleoside adenosine are reduced in patients with primary aldosteronism without affecting ischaemia‐reperfusion injury: A prospective case‐control study |
title | Plasma levels of the cardiovascular protective endogenous nucleoside adenosine are reduced in patients with primary aldosteronism without affecting ischaemia‐reperfusion injury: A prospective case‐control study |
title_full | Plasma levels of the cardiovascular protective endogenous nucleoside adenosine are reduced in patients with primary aldosteronism without affecting ischaemia‐reperfusion injury: A prospective case‐control study |
title_fullStr | Plasma levels of the cardiovascular protective endogenous nucleoside adenosine are reduced in patients with primary aldosteronism without affecting ischaemia‐reperfusion injury: A prospective case‐control study |
title_full_unstemmed | Plasma levels of the cardiovascular protective endogenous nucleoside adenosine are reduced in patients with primary aldosteronism without affecting ischaemia‐reperfusion injury: A prospective case‐control study |
title_short | Plasma levels of the cardiovascular protective endogenous nucleoside adenosine are reduced in patients with primary aldosteronism without affecting ischaemia‐reperfusion injury: A prospective case‐control study |
title_sort | plasma levels of the cardiovascular protective endogenous nucleoside adenosine are reduced in patients with primary aldosteronism without affecting ischaemia‐reperfusion injury: a prospective case‐control study |
topic | Original Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6900001/ https://www.ncbi.nlm.nih.gov/pubmed/31659743 http://dx.doi.org/10.1111/eci.13180 |
work_keys_str_mv | AT vandenbergtnadanielle plasmalevelsofthecardiovascularprotectiveendogenousnucleosideadenosinearereducedinpatientswithprimaryaldosteronismwithoutaffectingischaemiareperfusioninjuryaprospectivecasecontrolstudy AT thijssendickhj plasmalevelsofthecardiovascularprotectiveendogenousnucleosideadenosinearereducedinpatientswithprimaryaldosteronismwithoutaffectingischaemiareperfusioninjuryaprospectivecasecontrolstudy AT vanmilankeccm plasmalevelsofthecardiovascularprotectiveendogenousnucleosideadenosinearereducedinpatientswithprimaryaldosteronismwithoutaffectingischaemiareperfusioninjuryaprospectivecasecontrolstudy AT vandenbroekpetrah plasmalevelsofthecardiovascularprotectiveendogenousnucleosideadenosinearereducedinpatientswithprimaryaldosteronismwithoutaffectingischaemiareperfusioninjuryaprospectivecasecontrolstudy AT rongengerarda plasmalevelsofthecardiovascularprotectiveendogenousnucleosideadenosinearereducedinpatientswithprimaryaldosteronismwithoutaffectingischaemiareperfusioninjuryaprospectivecasecontrolstudy AT monajemihoushang plasmalevelsofthecardiovascularprotectiveendogenousnucleosideadenosinearereducedinpatientswithprimaryaldosteronismwithoutaffectingischaemiareperfusioninjuryaprospectivecasecontrolstudy AT deinumjaap plasmalevelsofthecardiovascularprotectiveendogenousnucleosideadenosinearereducedinpatientswithprimaryaldosteronismwithoutaffectingischaemiareperfusioninjuryaprospectivecasecontrolstudy AT riksennielsp plasmalevelsofthecardiovascularprotectiveendogenousnucleosideadenosinearereducedinpatientswithprimaryaldosteronismwithoutaffectingischaemiareperfusioninjuryaprospectivecasecontrolstudy |