Colchicine enhances β adrenoceptor-mediated vasodilation in men with essential hypertension.
Kv7-channel
colchicine
essential hypertension
Journal
British journal of clinical pharmacology
ISSN: 1365-2125
Titre abrégé: Br J Clin Pharmacol
Pays: England
ID NLM: 7503323
Informations de publication
Date de publication:
07 2023
07 2023
Historique:
revised:
20
12
2022
received:
21
09
2022
accepted:
05
01
2023
medline:
19
6
2023
pubmed:
11
2
2023
entrez:
10
2
2023
Statut:
ppublish
Résumé
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. 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. 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. 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. 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.
Substances chimiques
Nitroprusside
169D1260KM
Isoproterenol
L628TT009W
Acetylcholine
N9YNS0M02X
Colchicine
SML2Y3J35T
Receptors, Adrenergic
0
Banques de données
ClinicalTrials.gov
['NCT04303689']
Types de publication
Randomized Controlled Trial
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2179-2189Informations de copyright
© 2023 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.
Références
Ghalioungui P. The Ebers Papyrus: A New English Translation, Commentaries and Glossaries. 1987th ed. Academy of Scientific Research and Technology; n.d.
Pelletier P, Caventou J. Examen chimique de plusieurs végétaux de la famille des colchicées et du principe actif qu'ils renferment. Ann Chim Phys. 1820;14:69-83.
Hemkens LG, Ewald H, Gloy VL, et al. Colchicine for prevention of cardiovascular events. Cochrane Database Syst Rev. 2016;2016(1):CD011047. doi:10.1002/14651858.CD011047.PUB2
Kofler T, Kurmann R, Lehnick D, et al. Colchicine in patients with coronary artery disease: a systematic review and meta-analysis of randomized trials. J Am Heart Assoc. 2021;10(16):e021198. doi:10.1161/JAHA.121.021198
Deftereos SG, Beerkens FJ, Shah B, et al. Colchicine in cardiovascular disease: in-depth review. Circulation. 2022;145(1):61-78. doi:10.1161/CIRCULATIONAHA.121.056171
Samuel M, Tardif JC, Bouabdallaoui N, et al. Colchicine for secondary prevention of cardiovascular disease: a systematic review and meta-analysis of randomized controlled trials. Can J Cardiol. 2021;37(5):776-785. doi:10.1016/J.CJCA.2020.10.006
Martínez GJ, Celermajer DS, Patel S. The NLRP3 inflammasome and the emerging role of colchicine to inhibit atherosclerosis-associated inflammation. Atherosclerosis. 2018;269:262-271. doi:10.1016/J.ATHEROSCLEROSIS.2017.12.027
Kajikawa M, Higashi Y, Tomiyama H, et al. Effect of short-term colchicine treatment on endothelial function in patients with coronary artery disease. Int J Cardiol. 2019;281:35-39. doi:10.1016/J.IJCARD.2019.01.054
Lindman J, Khammy MM, Lundegaard PR, Aalkjr C, Jepps TA. Microtubule regulation of Kv7 channels orchestrates cAMP-mediated vasorelaxations in rat arterial smooth muscle. Hypertension. 2018;71(2):336-345. doi:10.1161/HYPERTENSIONAHA.117.10152
van der Horst J, Rognant S, Hellsten Y, Aalkjaer C, Jepps TA. Dynein coordinates β2-adrenoceptor-mediated relaxation in normotensive and hypertensive rat mesenteric arteries. Hypertension. 2022;79(10):2214-2227. doi:10.1161/HYPERTENSIONAHA.122.19351
Zhang D, Jin N, Rhoades RA, Yancey KW, Swartz DR. Influence of microtubules on vascular smooth muscle contraction. J Muscle Res Cell Motil. 2000;21(3):293-300. doi:10.1023/A:1005600118157
Chaldakov GN. Colchicine, a microtubule-disassembling drug, in the therapy of cardiovascular diseases. Cell Biol Int. 2018;42(8):1079-1084. doi:10.1002/CBIN.10988
Chadha PS, Zunke F, Zhu HL, et al. Reduced KCNQ4-encoded voltage-dependent potassium channel activity underlies impaired β-adrenoceptor-mediated relaxation of renal arteries in hypertension. Hypertension. 2012;59(4):877-884. doi:10.1161/HYPERTENSIONAHA.111.187427
Jepps TA, Chadha PS, Davis AJ, et al. Downregulation of Kv7.4 channel activity in primary and secondary hypertension. Circulation. 2011;124(5):602-611. doi:10.1161/CIRCULATIONAHA.111.032136
Werstiuk ES, Lee RMKW. Vascular beta-adrenoceptor function in hypertension and in ageing. Can J Physiol Pharmacol. 2000;78(6):433-452. doi:10.1139/y00-015
Cardillo C, Kilcoyne CM, Quyyumi AA, Cannon RO, Panza JA. Decreased vasodilator response to isoproterenol during nitric oxide inhibition in humans. Hypertension. 1997;30(4):918-921. doi:10.1161/01.HYP.30.4.918
Rochdi M, Sabouraud A, Girre C, Venet R, Scherrmann JM. Pharmacokinetics and absolute bioavailability of colchicine after i.v. and oral administration in healthy human volunteers and elderly subjects. Eur J Clin Pharmacol. 1994;46(4):351-354. doi:10.1007/BF00194404
Achtert G, Scherrmann JM, Christen MO. Pharmacokinetics/bioavailability of colchicine in healthy male volunteers. Eur J Drug Metab Pharmacokinet. 1989;14(4):317-322. doi:10.1007/BF03190118
Molad Y. Update on colchicine and its mechanism of action. Curr Rheumatol Rep. 2002;4(3):252-256. doi:10.1007/S11926-002-0073-2
Rytter N, Carter H, Piil P, et al. Ischemic preconditioning improves microvascular endothelial function in remote vasculature by enhanced prostacyclin production. J Am Heart Assoc. 2020;9(15):e016017. doi:10.1161/JAHA.120.016017
Stott JB, Barrese V, Greenwood IA. Kv7 channel activation underpins EPAC-dependent relaxations of rat arteries. Arterioscler Thromb Vasc Biol. 2016;36(12):2404-2411. doi:10.1161/ATVBAHA.116.308517
Mani BK, Robakowski C, Brueggemann LI, et al. Kv7.5 potassium channel subunits are the primary targets for PKA-dependent enhancement of vascular smooth muscle Kv7 currents. Mol Pharmacol. 2016;89(3):323-334. doi:10.1124/MOL.115.101758
van der Horst J, Greenwood IA, Jepps TA. Cyclic AMP-dependent regulation of Kv7 voltage-gated potassium channels. Front Physiol. 2020;11:11. doi:10.3389/FPHYS.2020.00727
Khanamiri S, Soltysinska E, Jepps TA, et al. Contribution of Kv7 channels to basal coronary flow and active response to ischemia. Hypertension. 2013;62(6):1090-1097. doi:10.1161/HYPERTENSIONAHA.113.01244
Chadha PS, Jepps TA, Carr G, et al. Contribution of kv7.4/kv7.5 heteromers to intrinsic and calcitonin gene-related peptide-induced cerebral reactivity. Arterioscler Thromb Vasc Biol. 2014;34(4):887-893. doi:10.1161/ATVBAHA.114.303405
van der Horst J, Rognant S, Abbott GW, et al. Dynein regulates Kv7.4 channel trafficking from the cell membrane. J Gen Physiol. 2021;153(3):e202012760. doi:10.1085/JGP.202012760
Stott JB, Barrese V, Jepps TA, Leighton E, Greenwood IA. Contribution of Kv7 channels to natriuretic peptide mediated vasodilation in normal and hypertensive rats. Hypertension. 2015;65(3):676-682. doi:10.1161/HYPERTENSIONAHA.114.04373
Mondéjar-Parreño G, Moral-Sanz J, Barreira B, et al. Activation of K v 7 channels as a novel mechanism for NO/cGMP-induced pulmonary vasodilation. Br J Pharmacol. 2019;176(13):2131-2145. doi:10.1111/BPH.14662
Hellsten Y, Nyberg M, Jensen LG, Mortensen SP. Vasodilator interactions in skeletal muscle blood flow regulation. J Physiol. 2012;590(24):6297-6305. doi:10.1113/JPHYSIOL.2012.240762
Lamontagne D, König A, Bassenge E, Busse R. Prostacyclin and nitric oxide contribute to the vasodilator action of acetylcholine and bradykinin in the intact rabbit coronary bed. J Cardiovasc Pharmacol. 1992;20(4):652-657. doi:10.1097/00005344-199210000-00020
Araújo A, Ferezin CZ, Rodrigues GJ, et al. Prostacyclin, not only nitric oxide, is a mediator of the vasorelaxation induced by acetylcholine in aortas from rats submitted to cecal ligation and perforation (CLP). Vascul Pharmacol. 2011;54(1-2):44-51. doi:10.1016/J.VPH.2010.12.002
Lagrue G, Wegrowski J, Rhabar K, et al. Effect of colchicine on atherosclerosis. I. Clinical and biological studies. Clin Physiol. Biochem. 1985;3(5):221-225.