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

Thomas S. Ehlers, Jennifer van der Horst, Sophie Møller, Peter K. Piil, Lasse Gliemann, Christian Aalkjær, Thomas A. Jepps, Ylva Hellsten*

*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

Abstract

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 washout period did not induce an accumulated or sustained effect on the β adrenoceptor response, and there was no effect on arterial pressure, arterial compliance or the level of measured inflammatory markers. Conclusion: 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. Condensed abstract: Preclinical studies in isolated rodent arteries have shown that colchicine can enhance β adrenoceptor-mediated vasodilation. Here we show that this effect of colchicine can be translated to humans. Acute colchicine treatment was found to increase both isoprenaline- and sodium nitroprusside-induced vasodilation. The study provides the first translational evidence for a transient β adrenoceptor-mediated vasodilatory effect of colchicine in humans. The finding of an acute effect suggests that it may be clinically important to maintain an adequate bioavailability of colchicine.

OriginalsprogEngelsk
TidsskriftBritish Journal of Clinical Pharmacology
Vol/bind89
Nummer7
Sider (fra-til)2179-2189
Antal sider11
ISSN0306-5251
DOI
StatusUdgivet - jul. 2023

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