TY - JOUR

T1 - Colchicine enhances β adrenoceptor-mediated vasodilation in men with essential hypertension

AU - Ehlers, Thomas Svare

AU - van der Horst, Jennifer

AU - Møller, Sophie

AU - Piil, Peter Kromann

AU - Gliemann, Lasse

AU - Aalkjær, Christian

AU - Jepps, Thomas A

AU - Hellsten, Ylva

N1 - This article is protected by copyright. All rights reserved.

PY - 2023

Y1 - 2023

N2 - Aims: The aim of this study is to examine whether colchicine improves β adrenoceptor-mediated vasodilation in humans by conducting a double-blinded, placebo-controlled intervention study. Colchicine treatment has known beneficial effects on cardiovascular health and reduces the incidence of cardiovascular disease. Studies in isolated rodent arteries have shown that colchicine can enhance β adrenoceptor-mediated vasodilation, but this has not been determined in humans.Methods: Middle-aged men with essential hypertension were randomly assigned firstly to acute treatment with either 0.5 mg colchicine (n=19) or placebo (n=12). They were subsequently re-randomized for 3 weeks of treatment with either colchicine 0.5 mg twice daily (n=16) or placebo (n=15) followed by a washout period of 48-72 h. The vasodilator responses to isoprenaline, acetylcholine and sodium nitroprusside were determined as well as arterial pressure, arterial compliance and plasma inflammatory markers.Results: Acute colchicine treatment increased isoprenaline (by 38% for the highest dose) as well as sodium nitroprusside (by 29% main effect) -induced vasodilation but had no effect on the response to acetylcholine. The 3-week colchicine treatment followed by a wash-out period did not induce an accumulated or sustained effect on the β adrenoceptor response, and there was no effect on either arterial pressure, arterial compliance or the level of measured inflammatory markers.Conclusions: Colchicine acutely enhances β adrenoceptor- and nitric oxide-mediated changes in vascular conductance in humans, supporting that the mechanism previously demonstrated in rodents, translates to humans. The results provide novel translational evidence for a transient enhancing effect of colchicine on β adrenoceptor-mediated vasodilation in humans with essential hypertension.

AB - Aims: The aim of this study is to examine whether colchicine improves β adrenoceptor-mediated vasodilation in humans by conducting a double-blinded, placebo-controlled intervention study. Colchicine treatment has known beneficial effects on cardiovascular health and reduces the incidence of cardiovascular disease. Studies in isolated rodent arteries have shown that colchicine can enhance β adrenoceptor-mediated vasodilation, but this has not been determined in humans.Methods: Middle-aged men with essential hypertension were randomly assigned firstly to acute treatment with either 0.5 mg colchicine (n=19) or placebo (n=12). They were subsequently re-randomized for 3 weeks of treatment with either colchicine 0.5 mg twice daily (n=16) or placebo (n=15) followed by a washout period of 48-72 h. The vasodilator responses to isoprenaline, acetylcholine and sodium nitroprusside were determined as well as arterial pressure, arterial compliance and plasma inflammatory markers.Results: Acute colchicine treatment increased isoprenaline (by 38% for the highest dose) as well as sodium nitroprusside (by 29% main effect) -induced vasodilation but had no effect on the response to acetylcholine. The 3-week colchicine treatment followed by a wash-out period did not induce an accumulated or sustained effect on the β adrenoceptor response, and there was no effect on either arterial pressure, arterial compliance or the level of measured inflammatory markers.Conclusions: Colchicine acutely enhances β adrenoceptor- and nitric oxide-mediated changes in vascular conductance in humans, supporting that the mechanism previously demonstrated in rodents, translates to humans. The results provide novel translational evidence for a transient enhancing effect of colchicine on β adrenoceptor-mediated vasodilation in humans with essential hypertension.

KW - Faculty of Science

KW - Essential hypertension

KW - Colchicine

KW - Kv7-channel

U2 - 10.1111/bcp.15688

DO - 10.1111/bcp.15688

M3 - Journal article

C2 - 36764326

VL - 89

SP - 2179

EP - 2189

JO - British Journal of Clinical Pharmacology, Supplement

JF - British Journal of Clinical Pharmacology, Supplement

SN - 0264-3774

IS - 7

ER -