Impaired β 2 -adrenergic endothelium-dependent vasodilation in patients previously hospitalized with coronavirus disease 2019

Luca Faconti; Bushra Farukh; Ryan J McNally; Sally Brett; Phil J Chowienczyk

doi:10.1097/HJH.0000000000003420

Impaired β 2 -adrenergic endothelium-dependent vasodilation in patients previously hospitalized with coronavirus disease 2019

Luca Faconti, Bushra Farukh, Ryan J McNally, Sally Brett, Phil J Chowienczyk

Research output: Contribution to journal › Article › peer-review

2 Citations (Scopus)

Abstract

AIM: The pulse wave response to salbutamol (PWRS) - change in augmentation index (AIx) - provides a means to assess endothelial vasodilator function in vivo . Endothelial dysfunction plays a relevant role in the pathogenesis of hypertension and cardiovascular disease and appears to underlie many of the complications of coronavirus disease 2019 (COVID-19). However, to what degree this persists after recovery is unknown.

METHODS: Individuals previously hospitalized with COVID-19, those recovered from mild symptoms and seronegative controls with well known risk factors for endothelial dysfunction were studied. To assess the involvement of nitric oxide-cyclic guanosine monophosphate pathway (NO-cGMP) on PWRS, sildenafil was also administrated in a subsample.

RESULTS: One hundred and one participants (60 men) aged 47.8 ± 14.1 (mean ± SD) years of whom 33 were previously hospitalized with COVID-19 were recruited. Salbutamol had minimal effect on haemodynamics including blood pressure and heart rate. It reduced AIx in controls ( n = 34) and those recovered from mild symptoms of COVID-19 ( n = 34) but produced an increase in AIx in those previously hospitalized: mean change [95% confidence interval] -2.85 [-5.52, -0.188] %, -2.32 [-5.17,0.54] %, and 3.03 [0.06, 6.00] % for controls, those recovered from mild symptoms and those previously hospitalized, respectively ( P = 0.001). In a sub-sample ( n = 22), sildenafil enhanced PWRS (change in AIx 0.05 [-2.15,2.24] vs. -3.96 [-7.01. -2.18], P = 0.006) with no significant difference between hospitalized ( n = 12) and nonhospitalized participants ( n = 10).

CONCLUSIONS: In patients previously hospitalized with COVID-19, there is long-lasting impairment of endothelial function as measured by the salbutamol-induced stimulation of the NO-cGMP pathway that may contribute to cardiovascular complications.

Original language	English
Pages (from-to)	951-957
Number of pages	7
Journal	Journal of hypertension
Volume	41
Issue number	6
DOIs	https://doi.org/10.1097/HJH.0000000000003420
Publication status	Published - 1 Jun 2023

Keywords

Male
Humans
Vasodilation
Sildenafil Citrate/pharmacology
Adrenergic Agents/pharmacology
Endothelium, Vascular
COVID-19/complications
Vasodilator Agents/pharmacology
Albuterol/pharmacology
Hypertension

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1097/HJH.0000000000003420

Cite this

@article{2af16164f83948afbb99c6aa986b99ef,

title = "Impaired β 2 -adrenergic endothelium-dependent vasodilation in patients previously hospitalized with coronavirus disease 2019",

abstract = "AIM: The pulse wave response to salbutamol (PWRS) - change in augmentation index (AIx) - provides a means to assess endothelial vasodilator function in vivo . Endothelial dysfunction plays a relevant role in the pathogenesis of hypertension and cardiovascular disease and appears to underlie many of the complications of coronavirus disease 2019 (COVID-19). However, to what degree this persists after recovery is unknown.METHODS: Individuals previously hospitalized with COVID-19, those recovered from mild symptoms and seronegative controls with well known risk factors for endothelial dysfunction were studied. To assess the involvement of nitric oxide-cyclic guanosine monophosphate pathway (NO-cGMP) on PWRS, sildenafil was also administrated in a subsample.RESULTS: One hundred and one participants (60 men) aged 47.8 ± 14.1 (mean ± SD) years of whom 33 were previously hospitalized with COVID-19 were recruited. Salbutamol had minimal effect on haemodynamics including blood pressure and heart rate. It reduced AIx in controls ( n = 34) and those recovered from mild symptoms of COVID-19 ( n = 34) but produced an increase in AIx in those previously hospitalized: mean change [95% confidence interval] -2.85 [-5.52, -0.188] %, -2.32 [-5.17,0.54] %, and 3.03 [0.06, 6.00] % for controls, those recovered from mild symptoms and those previously hospitalized, respectively ( P = 0.001). In a sub-sample ( n = 22), sildenafil enhanced PWRS (change in AIx 0.05 [-2.15,2.24] vs. -3.96 [-7.01. -2.18], P = 0.006) with no significant difference between hospitalized ( n = 12) and nonhospitalized participants ( n = 10).CONCLUSIONS: In patients previously hospitalized with COVID-19, there is long-lasting impairment of endothelial function as measured by the salbutamol-induced stimulation of the NO-cGMP pathway that may contribute to cardiovascular complications.",

keywords = "Male, Humans, Vasodilation, Sildenafil Citrate/pharmacology, Adrenergic Agents/pharmacology, Endothelium, Vascular, COVID-19/complications, Vasodilator Agents/pharmacology, Albuterol/pharmacology, Hypertension",

author = "Luca Faconti and Bushra Farukh and McNally, {Ryan J} and Sally Brett and Chowienczyk, {Phil J}",

note = "Copyright {\textcopyright} 2023 Wolters Kluwer Health, Inc. All rights reserved. Funding Information: Sources of funding: This work was supported by financial support from the Department of Health via the National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre and Clinical Research Facilities awards to Guy's and St Thomas{\textquoteright} NHS Foundation Trust in partnership with King's College London and King's College Hospital NHS Foundation Trust. Publisher Copyright: {\textcopyright} 2023 Lippincott Williams and Wilkins. All rights reserved.",

year = "2023",

month = jun,

day = "1",

doi = "10.1097/HJH.0000000000003420",

language = "English",

volume = "41",

pages = "951--957",

journal = "Journal of hypertension",

issn = "0263-6352",

publisher = "LIPPINCOTT WILLIAMS & WILKINS",

number = "6",

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TY - JOUR

T1 - Impaired β 2 -adrenergic endothelium-dependent vasodilation in patients previously hospitalized with coronavirus disease 2019

AU - Faconti, Luca

AU - Farukh, Bushra

AU - McNally, Ryan J

AU - Brett, Sally

AU - Chowienczyk, Phil J

N1 - Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved. Funding Information: Sources of funding: This work was supported by financial support from the Department of Health via the National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre and Clinical Research Facilities awards to Guy's and St Thomas’ NHS Foundation Trust in partnership with King's College London and King's College Hospital NHS Foundation Trust. Publisher Copyright: © 2023 Lippincott Williams and Wilkins. All rights reserved.

PY - 2023/6/1

Y1 - 2023/6/1

N2 - AIM: The pulse wave response to salbutamol (PWRS) - change in augmentation index (AIx) - provides a means to assess endothelial vasodilator function in vivo . Endothelial dysfunction plays a relevant role in the pathogenesis of hypertension and cardiovascular disease and appears to underlie many of the complications of coronavirus disease 2019 (COVID-19). However, to what degree this persists after recovery is unknown.METHODS: Individuals previously hospitalized with COVID-19, those recovered from mild symptoms and seronegative controls with well known risk factors for endothelial dysfunction were studied. To assess the involvement of nitric oxide-cyclic guanosine monophosphate pathway (NO-cGMP) on PWRS, sildenafil was also administrated in a subsample.RESULTS: One hundred and one participants (60 men) aged 47.8 ± 14.1 (mean ± SD) years of whom 33 were previously hospitalized with COVID-19 were recruited. Salbutamol had minimal effect on haemodynamics including blood pressure and heart rate. It reduced AIx in controls ( n = 34) and those recovered from mild symptoms of COVID-19 ( n = 34) but produced an increase in AIx in those previously hospitalized: mean change [95% confidence interval] -2.85 [-5.52, -0.188] %, -2.32 [-5.17,0.54] %, and 3.03 [0.06, 6.00] % for controls, those recovered from mild symptoms and those previously hospitalized, respectively ( P = 0.001). In a sub-sample ( n = 22), sildenafil enhanced PWRS (change in AIx 0.05 [-2.15,2.24] vs. -3.96 [-7.01. -2.18], P = 0.006) with no significant difference between hospitalized ( n = 12) and nonhospitalized participants ( n = 10).CONCLUSIONS: In patients previously hospitalized with COVID-19, there is long-lasting impairment of endothelial function as measured by the salbutamol-induced stimulation of the NO-cGMP pathway that may contribute to cardiovascular complications.

AB - AIM: The pulse wave response to salbutamol (PWRS) - change in augmentation index (AIx) - provides a means to assess endothelial vasodilator function in vivo . Endothelial dysfunction plays a relevant role in the pathogenesis of hypertension and cardiovascular disease and appears to underlie many of the complications of coronavirus disease 2019 (COVID-19). However, to what degree this persists after recovery is unknown.METHODS: Individuals previously hospitalized with COVID-19, those recovered from mild symptoms and seronegative controls with well known risk factors for endothelial dysfunction were studied. To assess the involvement of nitric oxide-cyclic guanosine monophosphate pathway (NO-cGMP) on PWRS, sildenafil was also administrated in a subsample.RESULTS: One hundred and one participants (60 men) aged 47.8 ± 14.1 (mean ± SD) years of whom 33 were previously hospitalized with COVID-19 were recruited. Salbutamol had minimal effect on haemodynamics including blood pressure and heart rate. It reduced AIx in controls ( n = 34) and those recovered from mild symptoms of COVID-19 ( n = 34) but produced an increase in AIx in those previously hospitalized: mean change [95% confidence interval] -2.85 [-5.52, -0.188] %, -2.32 [-5.17,0.54] %, and 3.03 [0.06, 6.00] % for controls, those recovered from mild symptoms and those previously hospitalized, respectively ( P = 0.001). In a sub-sample ( n = 22), sildenafil enhanced PWRS (change in AIx 0.05 [-2.15,2.24] vs. -3.96 [-7.01. -2.18], P = 0.006) with no significant difference between hospitalized ( n = 12) and nonhospitalized participants ( n = 10).CONCLUSIONS: In patients previously hospitalized with COVID-19, there is long-lasting impairment of endothelial function as measured by the salbutamol-induced stimulation of the NO-cGMP pathway that may contribute to cardiovascular complications.

KW - Male

KW - Humans

KW - Vasodilation

KW - Sildenafil Citrate/pharmacology

KW - Adrenergic Agents/pharmacology

KW - Endothelium, Vascular

KW - COVID-19/complications

KW - Vasodilator Agents/pharmacology

KW - Albuterol/pharmacology

KW - Hypertension

UR - http://www.scopus.com/inward/record.url?scp=85158865887&partnerID=8YFLogxK

U2 - 10.1097/HJH.0000000000003420

DO - 10.1097/HJH.0000000000003420

M3 - Article

C2 - 37016904

SN - 0263-6352

VL - 41

SP - 951

EP - 957

JO - Journal of hypertension

JF - Journal of hypertension

IS - 6

ER -

Impaired β 2 -adrenergic endothelium-dependent vasodilation in patients previously hospitalized with coronavirus disease 2019

Abstract

Keywords

UN SDGs

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