Chronic cannabidiol treatment induces cardiovascular improvement in renovascular hypertensive rats.
Journal
Journal of hypertension
ISSN: 1473-5598
Titre abrégé: J Hypertens
Pays: Netherlands
ID NLM: 8306882
Informations de publication
Date de publication:
30 Sep 2024
30 Sep 2024
Historique:
received:
10
04
2024
accepted:
23
08
2024
medline:
1
10
2024
pubmed:
1
10
2024
entrez:
1
10
2024
Statut:
aheadofprint
Résumé
Cannabidiol (CBD) is increasingly studied for its therapeutic potential in neurodegenerative diseases. Previous research on acute CBD administration has demonstrated cardiovascular benefits in hypertensive rats, including reduced mean blood pressure and oxidative stress. To investigate the long-term cardiovascular effects of chronic CBD treatment in renovascular hypertension induced by the 2-kidney-1-clip (2K1C) model. Male Wistar rats (180-200 g, 8 weeks old) underwent 2K1C or SHAM surgery. Six weeks later, rats received chronic CBD treatment (20 mg/kg, twice daily for 14 days). A combination of ex vivo, in vitro, and in vivo methods was used to assess CBD's cardiovascular effects in 2K1C hypertensive rats. Chronic CBD treatment significantly reduced blood pressure and the depressor response to hexamethonium (a ganglionic blocker). It also normalized variability in low-frequency (LF) power and LF/high-frequency (HF) ratio. CBD enhanced vasodilation and reduced vasoconstriction in the mesenteric artery of 2K1C rats, accompanied by decreased expression of aortic reactive oxygen species (ROS). Our findings suggest that chronic CBD treatment exerts antihypertensive effects by improving baroreflex sensitivity and vascular function while decreasing arterial ROS levels and sympathetic nerve activity. These results underscore CBD's potential therapeutic role in managing cardiovascular complications associated with renovascular hypertension.
Sections du résumé
BACKGROUND
BACKGROUND
Cannabidiol (CBD) is increasingly studied for its therapeutic potential in neurodegenerative diseases. Previous research on acute CBD administration has demonstrated cardiovascular benefits in hypertensive rats, including reduced mean blood pressure and oxidative stress.
AIM
OBJECTIVE
To investigate the long-term cardiovascular effects of chronic CBD treatment in renovascular hypertension induced by the 2-kidney-1-clip (2K1C) model.
METHODS
METHODS
Male Wistar rats (180-200 g, 8 weeks old) underwent 2K1C or SHAM surgery. Six weeks later, rats received chronic CBD treatment (20 mg/kg, twice daily for 14 days). A combination of ex vivo, in vitro, and in vivo methods was used to assess CBD's cardiovascular effects in 2K1C hypertensive rats.
RESULTS
RESULTS
Chronic CBD treatment significantly reduced blood pressure and the depressor response to hexamethonium (a ganglionic blocker). It also normalized variability in low-frequency (LF) power and LF/high-frequency (HF) ratio. CBD enhanced vasodilation and reduced vasoconstriction in the mesenteric artery of 2K1C rats, accompanied by decreased expression of aortic reactive oxygen species (ROS).
CONCLUSION
CONCLUSIONS
Our findings suggest that chronic CBD treatment exerts antihypertensive effects by improving baroreflex sensitivity and vascular function while decreasing arterial ROS levels and sympathetic nerve activity. These results underscore CBD's potential therapeutic role in managing cardiovascular complications associated with renovascular hypertension.
Identifiants
pubmed: 39351852
doi: 10.1097/HJH.0000000000003865
pii: 00004872-990000000-00554
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.
Références
World Health Organization. World Health Organization annual report 2019. WHO; 2019.
Zhou B, Carrillo-Larco RM, Danaei G, Riley LM, Paciorek CJ, Stevens GA, et al. Worldwide trends in hypertension prevalence and progress in treatment and control from 1990 to 2019: a pooled analysis of 1201 population-representative studies with 104 million participants. Lancet 2021; 398:957–980.
Mancia G, Kreutz R, Brunström M, Burnier M, Grassi G, Januszewicz A, et al. 2023 ESH Guidelines for the management of arterial hypertension the Task Force for the management of arterial hypertension of the European Society of Hypertension. J Hypertens 2023; 41:1874–2071.
Charles L, Triscott J, Dobbs B. Secondary hypertension: discovering the underlying cause. Am Fam Physician 2017; 96:453–461.
Sarathy H, Salman LA, Lee C, Cohen JB. Evaluation and management of secondary hypertension. Med Clin North Am 2022; 106:269–283.
Garovic VD, Kane GC, Schwartz GL. Renovascular hypertension: balancing the controversies in diagnosis and treatment. Cleve Clin J Med 2005; 72:1135–1144.
Rossi GP, Bisogni V, Rossitto G, Maiolino G, Cesari M, Zhu R, et al. Practice recommendations for diagnosis and treatment of the most common forms of secondary hypertension. High Blood Press Cardiovasc Prev 2020; 27:547–560.
Hansen KJ, Edwards MS, Craven TE, Cherr GS, Jackson SA, Appel RG, et al. Prevalence of renovascular disease in the elderly: a population-based study. J Vasc Surg 2002; 36:443–451.
Rimoldi SF, Scherrer U, Messerli FH. Secondary arterial hypertension: when, who, and how to screen? Eur Heart J 2014; 35:1245–1254.
Johansson M, Elam M, Rundqvist B, Eisenhofer G, Herlitz H, Lambert G, et al. Increased sympathetic nerve activity in renovascular hypertension. Circulation 1999; 99:2537–2542.
Herrmann SM, Textor SC. Current concepts in the treatment of renovascular hypertension. Am J Hypertens 2018; 31:139–149.
Persu A, Canning C, Prejbisz A, Dobrowolski P, Amar L, Chrysochou C, et al. Beyond atherosclerosis and fibromuscular dysplasia: rare causes of renovascular hypertension. Hypertension 2021; 78:898–911.
Losito A, Fagugli R, Zampi I, Parente B, Derango P, Giordano G, et al. Comparison of target organ damage in renovascular and essential hypertension. Am J Hypertens 1996; 9:1062–1067.
Benjamin MM, Fazel P, Filardo G, Choi JW, Stoler RC. Prevalence of and risk factors of renal artery stenosis in patients with resistant hypertension. Am J Cardiol 2014; 113:687–690.
de Bhailis ÁM, Lake E, Chrysochou C, Green D, Chinnadurai R, Kalra PA. Improving outcomes in atherosclerotic renovascular disease: importance of clinical presentation and multidisciplinary review. J Nephrol 2024; 37:1093–1105.
Textor SC. Renal arterial disease and hypertension. Med Clin N Am 2017; 101:65–79.
Goldblatt H, Lynch J, Hanzal RF, Summerville WW. Studies on experimental hypertension. J Exp Med 1934; 59:347–379.
Blanch GT, Freiria-Oliveira AH, Speretta GFF, Carrera EJ, Li H, Speth RC, et al. Increased expression of angiotensin II type 2 receptors in the solitary-vagal complex blunts renovascular hypertension. Hypertension 2014; 64:777–783.
Shimoura CG, Lincevicius GS, Nishi EE, Girardi ACC, Simon KA, Bergamaschi CT, et al. Increased dietary salt changes baroreceptor sensitivity and intrarenal renin-angiotensin system in Goldblatt hypertension. Am J Hypertens 2017; 30:28–36.
Roncari CF, Barbosa RM, Vendramini RC, De Luca LA Jr, Menani JV, Colombari E, et al. Enhanced angiotensin II induced sodium appetite in renovascular hypertensive rats. Peptides (NY) 2018; 101:82–88.
Melo MR, Gasparini S, Speretta GF, Silva EF, Rodrigues Pedrino G, Menani JV, et al. Importance of the commissural nucleus of the solitary tract in renovascular hypertension. Hypertens Res 2019; 42:587–597.
Setiadi A, Korim WS, May CN, Yao ST. Systemic administration of pentoxifylline attenuates the development of hypertension in renovascular hypertensive rats. Hypertens Res 2020; 43:667–678.
Lauar MR, Evans LC, Van Helden D, Fink GD, Banek CT, Menani JV, et al. Renal and hypothalamic inflammation in renovascular hypertension: role of afferent renal nerves. Am J Physiol Regul Integr Comp Physiol 2023; 325:R411–R422.
Kumric M, Dujic G, Vrdoljak J, Supe-Domic D, Bilopavlovic N, Dolic K, et al. Effects of CBD supplementation on ambulatory blood pressure and serum urotensin-II concentrations in Caucasian patients with essential hypertension: a sub-analysis of the HYPER-H21-4 trial. Biomed Pharmacother 2023; 164:115016.
Laprairie RB, Bagher AM, Kelly MEM, Denovan-Wright EM. Cannabidiol is a negative allosteric modulator of the cannabinoid CB 1 receptor. Br J Pharmacol 2015; 172:4790–4805.
Lucas CJ, Galettis P, Schneider J. The pharmacokinetics and the pharmacodynamics of cannabinoids. Br J Clin Pharmacol 2018; 84:2477–2482.
Atalay S, Jarocka-Karpowicz I, Skrzydlewska E. Antioxidative and anti-inflammatory properties of cannabidiol. Antioxidants 2019; 9:E21.
Remiszewski P, Jarocka-Karpowicz I, Biernacki M, Jastrząb A, Schlicker E, Toczek M, et al. Chronic cannabidiol administration fails to diminish blood pressure in rats with primary and secondary hypertension despite its effects on cardiac and plasma endocannabinoid system, oxidative stress and lipid metabolism. Int J Mol Sci 2020; 21:1295.
Remiszewski P, Malinowska B. Why multitarget vasodilatory (endo)cannabinoids are not effective as antihypertensive compounds after chronic administration: comparison of their effects on systemic and pulmonary hypertension. Pharmaceuticals 2022; 15:1119.
Stanley CP, Hind WH, O'Sullivan SE. Is the cardiovascular system a therapeutic target for cannabidiol? Br J Clin Pharmacol 2013; 75:313–322.
Stanley CP, Hind WH, Tufarelli C, O'Sullivan SE. Cannabidiol causes endothelium-dependent vasorelaxation of human mesenteric arteries via CB 1 activation. Cardiovasc Res 2015; 107:568–578.
Jadoon KA, Tan GD, O'Sullivan SE. A single dose of cannabidiol reduces blood pressure in healthy volunteers in a randomized crossover study. JCI Insight 2017; 2:93760.
Kossakowski R, Schlicker E, Toczek M, Weresa J, Malinowska B. Cannabidiol affects the Bezold-Jarisch reflex via TRPV1 and 5-HT3 receptors and has peripheral sympathomimetic effects in spontaneously hypertensive and normotensive rats. Front Pharmacol 2019; 10 doi:10.3389/fphar.2019.00500.
doi: 10.3389/fphar.2019.00500
Baranowska-Kuczko M, Kozłowska H, Kloza M, Kusaczuk M, Harasim-Symbor E, Biernacki M, et al. Vasoprotective endothelial effects of chronic cannabidiol treatment and its influence on the endocannabinoid system in rats with primary and secondary hypertension. Pharmaceuticals 2021; 14:1120.
Resstel LBM, Tavares RF, Lisboa SFS, Joca SRL, Corrêa FMA, Guimarães FS. 5-HT 1A receptors are involved in the cannabidiol-induced attenuation of behavioural and cardiovascular responses to acute restraint stress in rats. Br J Pharmacol 2009; 156:181–188.
Turu G, Simon A, Gyombolai P, Szidonya L, Bagdy G, Lenkei Z, et al. The role of diacylglycerol lipase in constitutive and angiotensin AT1 receptor-stimulated cannabinoid CB1 receptor activity. J Biol Chem 2007; 282:7753–7757.
Gyombolai P, Pap D, Turu G, Catt KJ, Bagdy G, Hunyady L. Regulation of endocannabinoid release by G proteins: a paracrine mechanism of G protein-coupled receptor action. Mol Cell Endocrinol 2012; 353:29–36.
Szekeres M, Nádasy GL, Turu G, Soltész-Katona E, Tóth ZE, Balla A, et al. Angiotensin II induces vascular endocannabinoid release, which attenuates its vasoconstrictor effect via CB1 cannabinoid receptors. J Biol Chem 2012; 287:31540–31550.
Szekeres M, Nádasy GL, Turu G, Soltész-Katona E, Benyó Z, Offermanns S, et al. Endocannabinoid-mediated modulation of Gq/11 protein-coupled receptor signaling-induced vasoconstriction and hypertension. Mol Cell Endocrinol 2015; 403:46–56.
Guo Z, Liu Y-X, Yuan F, Ma H-J, Maslov L, Zhang Y. Enhanced vasorelaxation effect of endogenous anandamide on thoracic aorta in renal vascular hypertension rats. Clin Exp Pharmacol Physiol 2015; 42:950–955.
Schaich CL, Shaltout HA, Brosnihan KB, Howlett AC, Diz DI. Acute and chronic systemic CB 1 cannabinoid receptor blockade improves blood pressure regulation and metabolic profile in hypertensive (mRen2)27 rats. Physiol Rep 2014; 2:e12108.
Mińczuk K, Baranowska-Kuczko M, Krzyżewska A, Schlicker E, Malinowska B. Cross-talk between the (endo)cannabinoid and renin-angiotensin systems: basic evidence and potential therapeutic significance. Int J Mol Sci 2022; 23:6350.
Bátkai S, Pacher P, Osei-Hyiaman D, Radaeva S, Liu J, Harvey-White J, et al. Endocannabinoids acting at cannabinoid-1 receptors regulate cardiovascular function in hypertension. Circulation 2004; 110:1996–2002.
Roncari CF, David RB, de Paula PM, Colombari DSA, de Luca LA, Menani JV. Importance of central AT 1 receptors for sodium intake induced by GABAergic activation of the lateral parabrachial nucleus. Neuroscience 2011; 196:147–152.
Nair A, Jacob S. A simple practice guide for dose conversion between animals and human. J Basic Clin Pharm 2016; 7:27.
Braga VA, Burmeister MA, Sharma RV, Davisson RL. Cardiovascular responses to peripheral chemoreflex activation and comparison of different methods to evaluate baroreflex gain in conscious mice using telemetry. Am J Physiol Regul Integr Comp Physiol 2008; 295:R1168–R1174.
Cruz JC, Bonagamba LGH, Machado BH, Biancardi VC, Stern JE. Intermittent activation of peripheral chemoreceptors in awake rats induces Fos expression in rostral ventrolateral medulla-projecting neurons in the paraventricular nucleus of the hypothalamus. Neuroscience 2008; 157:463–472.
Biancardi VC, Son SJ, Ahmadi S, Filosa JA, Stern JE. Circulating angiotensin II gains access to the hypothalamus and brain stem during hypertension via breakdown of the blood-brain barrier. Hypertension 2014; 63:572–579.
Miklós Z, Wafa D, Nádasy GL, Tóth ZE, Besztercei B, Dörnyei G, et al. Angiotensin II-induced cardiac effects are modulated by endocannabinoid-mediated CB1 receptor activation. Cells 2021; 10:724.
Tamaki C, Nawa H, Takatori S, Oda S, Sendo T, Zamami Y, et al. Anandamide induces endothelium-dependent vasoconstriction and CGRPergic nerve-mediated vasodilatation in the rat mesenteric vascular bed. J Pharmacol Sci 2012; 118:496–505.
Peng J, Li Y-J. The vanilloid receptor TRPV1: Role in cardiovascular and gastrointestinal protection. Eur J Pharmacol 2010; 627:1–7.
Herkenham M, Lynn A, Johnson M, Melvin L, de Costa B, Rice K. Characterization and localization of cannabinoid receptors in rat brain: a quantitative in vitro autoradiographic study. J Neurosci 1991; 11:563–583.
Seagard JL, Hopp FA, Hillard CJ, Dean C. Effects of endocannabinoids on discharge of baroreceptive NTS neurons. Neurosci Lett 2005; 381:334–339.
Chen C-Y, Bonham AC, Dean C, Hopp FA, Hillard CJ, Seagard JL. Retrograde release of endocannabinoids inhibits presynaptic GABA release to second-order baroreceptive neurons in NTS. Auton Neurosci 2010; 158:44–50.
Wang T, Li G-Q, Zhang H-P, Zhang Y, Li Q. Overactivation of cannabinoid receptor type 1 in rostral ventrolateral medulla promotes cardiovascular responses in spontaneously hypertensive rats. J Hypertens 2017; 35:538–545.
Liu B, Li Z, Zhang Y, Luo W, Zhang J, Li H, et al. Vasomotor reaction to cyclooxygenase-1-mediated prostacyclin synthesis in carotid arteries from two-kidney-one-clip hypertensive mice. PLoS One 2015; 10:e0136738.
Schaich CL, Grabenauer M, Thomas BF, Shaltout HA, Gallagher PE, Howlett AC, et al. Medullary endocannabinoids contribute to the differential resting baroreflex sensitivity in rats with altered brain renin-angiotensin system expression. Front Physiol 2016; 7:207.
Alves FHF, Crestani CC, Gomes FV, Guimarães FS, Correa FMA, Resstel LBM. Cannabidiol injected into the bed nucleus of the stria terminalis modulates baroreflex activity through 5-HT1A receptors. Pharmacol Res 2010; 62:228–236.
Batista LA, Haibara AS, Schenberg LC, Moreira FA. Effects of alprazolam and cannabinoid-related compounds in an animal model of panic attack. Behav Brain Res 2017; 317:508–514.
Casarotto PC, Terzian ALB, Aguiar DC, Zangrossi H, Guimarães FS, Wotjak CT, et al. Opposing roles for cannabinoid receptor type-1 (CB1) and transient receptor potential vanilloid type-1 channel (TRPV1) on the modulation of panic-like responses in rats. Neuropsychopharmacology 2012; 37:478–486.
Rajagopalan S, Kurz S, Münzel T, Tarpey M, Freeman BA, Griendling KK, et al. Angiotensin II-mediated hypertension in the rat increases vascular superoxide production via membrane NADH/NADPH oxidase activation. Contribution to alterations of vasomotor tone. J Clin Invest 1996; 97:1916–1923.
Han KH, Lim S, Ryu J, Lee C-W, Kim Y, Kang J-H, et al. CB1 and CB2 cannabinoid receptors differentially regulate the production of reactive oxygen species by macrophages. Cardiovasc Res 2009; 84:378–386.
Koenen M, Hill MA, Cohen P, Sowers JR. Obesity, adipose tissue and vascular dysfunction. Circ Res 2021; 128:951–968.