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

AimsThe aim of this study is to examine whether colchicine improves beta 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 beta adrenoceptor-mediated vasodilation, but this has not been determined in humans. MethodsMiddle-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. ResultsAcute 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 beta adrenoceptor response, and there was no effect on arterial pressure, arterial compliance or the level of measured inflammatory markers. ConclusionColchicine acutely enhances beta 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 beta adrenoceptor-mediated vasodilation in humans with essential hypertension. Condensed abstractPreclinical studies in isolated rodent arteries have shown that colchicine can enhance beta 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 beta 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.

Automated summary

The aim of this study was to investigate the effects of colchicine on beta adrenoceptor-mediated vasodilation in humans. The results showed that acute treatment with colchicine increased vasodilation induced by beta adrenoceptor agonist and nitric oxide in humans with essential hypertension. This finding has important implications for the treatment of hypertension.