Abstract
Background
Anti-hypertensive drugs can improve vascular endothelial function. However, the mechanism remains to be elucidated.
Objectives
This study sought to investigate mechanisms of anti-hypertensive drugs on improvement of vascular endothelial function in patients with essential hypertension.
Methods
Forty-five patients (mean age 58.5 ± 11.2 years) with uncontrolled essential hypertension were randomly assigned to receive olmesartan, an angiotensin II type 1 receptor blocker (ARB) (N = 23), or amlodipine, a calcium channel blocker (CCB) (N = 22), for 6 months. Endothelial function was evaluated by flow-mediated dilatation (FMD) of the brachial artery. Vascular inflammation was measured by blood-normalized standardized uptake value, known as a target-to-background ratio (TBR) within the carotid arteries using 18F-fluorodeoxyglucose-positron emission tomography combined with computed tomography.
Results
There were no significant differences of baseline clinical data between the ARB and CCB groups. Both anti-hypertensive drugs comparably lowered blood pressure and increased %FMD. TBR values were reduced by olmesartan (P < .001), while blood pressure variability was decreased by amlodipine (P = .004). Changes in %FMD from baseline (Δ%FMD) were inversely associated with ΔTBR in the olmesartan group (r = − .606, P = .003) and with Δsystolic blood pressure variability in the amlodipine group (r = − .434, P = .039).
Conclusion
Our study indicated that olmesartan and amlodipine could improve endothelial function in patients with essential hypertension in different manners, suppression of vascular inflammation, and decrease in blood pressure variability, respectively.
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Abbreviations
- NO:
-
Nitric oxide
- FMD:
-
Flow-mediated dilatation
- BP:
-
Blood pressure
- CCB:
-
Calcium channel blocker
- ACE:
-
Angiotensin-converting enzyme
- ARB:
-
Angiotensin II type 1 receptor blockers
- FDG-PET:
-
18F-fluorodeoxyglucose-positron emission tomography
- CT:
-
Computed tomography
- SD:
-
Standard deviation
- HbA1c :
-
Glycated hemoglobin
- hsCRP:
-
High-sensitivity C-reactive protein
- SUV:
-
Standardized uptake value
- TBR:
-
Target-to-background ratio
References
Ghiadoni L, Magagna A, Versari D, Kardasz I, Huang Y, Taddei S. Different effect of antihypertensive drugs on conduit artery endothelial function. Hypertension 2003;41:1281‐6.
Ras RT, Streppel MT, Draijer R, Zock PL. Flow-mediated dilation and cardiovascular risk prediction: A systematic review with meta-analysis. Int J Cardiol 2013;168:344‐51.
Corretti MC, Anderson TJ, Benjamin EJ, Celermajer D, Charbonneau F, Creager MA, et al. Guidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery: A report of the International Brachial Artery Reactivity Task Force. J Am Coll Cardiol. 2002;39:257‐65.
Panza JA, Quyyumi AA, Brush JE Jr, Epstein SE. Abnormal endothelium-dependent vascular relaxation in patients with essential hypertension. N Engl J Med 1990;323:22‐7.
Taddei S, Ghiadoni L, Virdis A, Salvetti A. Vasodilation to bradykinin is mediated by an ouabain-sensitive pathway as a compensatory mechanism for impaired nitric oxide availability in essential hypertensive patients. Circulation 1999;100:1400‐5.
Perticone F, Ceravolo R, Pujia A, Ventura G, Iacopino S, Scozzafava A, et al. Prognostic significance of endothelial dysfunction in hypertensive patients. Circulation 2001;104:191‐6.
Gokce N, Keaney JF Jr, Hunter LM, Watkins MT, Menzoian JO, Vita JA. Risk stratification for postoperative cardiovascular events via noninvasive assessment of endothelial function: A prospective study. Circulation 2002;105:1567‐72.
Iwatsubo H, Nagano M, Sakai T, Kumamoto K, Morita R, Higaki J, et al. Converting enzyme inhibitor improves forearm reactive hyperemia in essential hypertension. Hypertension 1997;29:286‐90.
Higashi Y, Sasaki S, Nakagawa K, Ueda T, Yoshimizu A, Kurisu S, et al. A comparison of angiotensin-converting enzyme inhibitors, calcium antagonists, beta-blockers and diuretic agents on reactive hyperemia in patients with essential hypertension: A multicenter study. J Am Coll Cardiol 2000;35:284‐91.
Taddei S, Virdis A, Ghiadoni L, Magagna A, Favilla S, Pompella A, et al. Restoration of nitric oxide availability after calcium antagonist treatment in essential hypertension. Hypertension 2001;37:943‐8.
Taddei S, Virdis A, Ghiadoni L, Magagna A, Pasini AF, Garbin U, et al. Effect of calcium antagonist or beta blockade treatment on nitric oxide-dependent vasodilation and oxidative stress in essential hypertensive patients. J Hypertens 2001;19:1379‐86.
Benndorf RA, Appel D, Maas R, Schwedhelm E, Wenzel UO, Böger RH. Telmisartan improves endothelial function in patients with essential hypertension. J Cardiovasc Pharmacol 2007;50:367‐71.
Honda A, Tahara N, Nitta Y, Tahara A, Igata S, Bekki M, et al. Vascular inflammation evaluated by [18F]-fluorodeoxyglucose-positron emission tomography/computed tomography is associated with endothelial dysfunction. Arterioscler Thromb Vasc Biol 2016;36:1980‐8.
Diaz KM, Veerabhadrappa P, Kashem MA, Feairheller DL, Sturgeon KM, Williamson ST, et al. Relationship of visit-to-visit and ambulatory blood pressure variability to vascular function in African Americans. Hypertens Res 2012;35:55‐61.
Unger T, Borghi C, Charchar F, Khan NA, Poulter NR, Prabhakaran D, et al. 2020 International Society of Hypertension global hypertension practice guidelines. J Hypertens 2020;38:982‐1004.
Umemura S, Arima H, Arima S, Asayama K, Dohi Y, Hirooka Y, et al. The Japanese Society of Hypertension Guidelines for the Management of Hypertension (JSH 2019). Hypertens Res 2019;42:1235‐481.
Hoelzel W, Weykamp C, Jeppsson JO, Miedema K, Barr JR, Goodall I, et al. IFCC reference system for measurement of hemoglobin A1c in human blood and the national standardization schemes in the United States, Japan, and Sweden: A method-comparison study. Clin Chem. 2004;50:166‐74.
Matsuo S, Imai E, Horio M, Yasuda Y, Tomita K, Nitta K, et al. Collaborators developing the Japanese equation for estimated GFR. Revised equations for estimated GFR from serum creatinine in Japan. Am J Kidney Dis. 2009;53:982‐92.
Celermajer DS, Sorensen KE, Gooch VM, Spiegelhalter DJ, Miller OI, Sullivan ID, et al. Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis. Lancet 1992;340:1111‐5.
Anderson TJ, Uehata A, Gerhard MD, Meredith IT, Knab S, Delagrange D, et al. Close relation of endothelial function in the human coronary and peripheral circulations. J Am Coll Cardiol 1995;26:1235‐41.
Muiesan ML, Salvetti M, Monteduro C, Rizzoni D, Zulli R, Corbellini C, et al. Effect of treatment on flow-dependent vasodilation of the brachial artery in essential hypertension. Hypertension 1999;33:575‐80.
Lieberman EH, Gerhard MD, Uehata A, Walsh BW, Selwyn AP, Ganz P, et al. Estrogen improves endothelium-dependent, flow-mediated vasodilation in postmenopausal women. Ann Intern Med 1994;121:936‐41.
Hornig B, Maier V, Drexler H. Physical training improves endothelial function in patients with chronic heart failure. Circulation 1996;93:210‐4.
Guzik TJ, Touyz RM. Oxidative stress, inflammation, and vascular aging in hypertension. Hypertension 2017;70:660‐7.
Holm T, Aukrust P, Andreassen AK, Ueland T, Brosstad F, Frøland SS, et al. Peripheral endothelial dysfunction in heart transplant recipients: possible role of proinflammatory cytokines. Clin Transplant 2000;14:218‐25.
O’Brien KD, McDonald TO, Chait A, Allen MD, Alpers CE. Neovascular expression of E-selectin, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 in human atherosclerosis and their relation to intimal leukocyte content. Circulation 1996;93:672‐82.
Zhang G, Liu Y, Qiu Y, Sun J, Zhou Z, Wang Z, et al. Circulating senescent angiogenic T cells are linked with endothelial dysfunction and systemic inflammation in hypertension. J Hypertens 2021;39:970‐8.
Ridker PM, Rifai N, Stampfer MJ, Hennekens CH. Plasma concentration of interleukin-6 and the risk of future myocardial infarction among apparently healthy men. Circulation 2000;101:1767‐72.
Ridker PM, Howard CP, Walter V, Everett B, Libby P, Hensen J, et al. Effects of interleukin-1β inhibition with canakinumab on hemoglobin A1c, lipids, C-reactive protein, interleukin-6, and fibrinogen: a phase IIb randomized, placebo-controlled trial. Circulation. 2012;126:2739‐48.
Ridker PM, Everett BM, Thuren T, MacFadyen JG, Chang WH, Ballantyne C, et al. Antiinflammatory therapy with canakinumab for atherosclerotic disease. N Engl J Med. 2017;377:1119‐31.
Ferrario CM, Strawn WB. Role of the renin-angiotensin-aldosterone system and proinflammatory mediators in cardiovascular disease. Am J Cardiol 2006;98:121‐8.
Schmieder RE, Hilgers KF, Schlaich MP, Schmidt BM. Renin-angiotensin system and cardiovascular risk. Lancet 2007;369:1208‐19.
Förstermann U. Oxidative stress in vascular disease: Causes, defense mechanisms and potential therapies. Nat Clin Pract Cardiovasc Med 2008;5:338‐549.
Androulakis ES, Tousoulis D, Papageorgiou N, Tsioufis C, Kallikazaros I, Stefanadis C. Essential hypertension: Is there a role for inflammatory mechanisms? Cardiol Rev 2009;17:216‐21.
Fliser D, Buchholz K, Haller H, EUropean Trial on Olmesartan and Pravastatin in Inflammation and Atherosclerosis (EUTOPIA) Investigators. Antiinflammatory effects of angiotensin II subtype 1 receptor blockade in hypertensive patients with microinflammation. Circulation 2004;110:1103–7.
Zhao Y, Fukao K, Zhao S, Watanabe A, Hamada T, Yamasaki K, et al. Irbesartan attenuates atherosclerosis in Watanabe heritable hyperlipidemic rabbits: noninvasive imaging of inflammation by 18F-fluorodeoxyglucose positron emission tomography. Mol Imaging. 2015. https://doi.org/10.2310/7290.2015.00004.
Oh M, Lee CW, Ahn JM, Park DW, Kang SJ, Lee SW, et al. Comparison of fimasartan and amlodipine therapy on carotid atherosclerotic plaque inflammation. Clin Cardiol 2019;42:241‐6.
Rabelo LA, Alenina N, Bader M. ACE2-angiotensin-(1–7)-Mas axis and oxidative stress in cardiovascular disease. Hypertens Res 2011;34:154‐60.
Savoia C, Arrabito E, Parente R, Nicoletti C, Madaro L, Battistoni A, et al. Mas receptor activation contributes to the improvement of nitric oxide bioavailability and vascular remodeling during chronic AT1R (angiotensin type-1 receptor) blockade in experimental hypertension. Hypertension 2020;76:1753‐61.
Tulenko TN, Laury-Kleintop L, Walter MF, Mason RP. Cholesterol, calcium and atherosclerosis: Is there a role for calcium channel blockers in atheroprotection? Int J Cardiol 1997;62:S55-66.
Zhang X, Hintze TH. Amlodipine releases nitric oxide from canine coronary microvessels: An unexpected mechanism of action of a calcium channel-blocking agent. Circulation 1998;97:576‐80.
Chrysant SG, Melino M, Karki S, Lee J, Heyrman R. The combination of olmesartan medoxomil and amlodipine besylate in controlling high blood pressure: COACH, a randomized, double-blind, placebo-controlled, 8-week factorial efficacy and safety study. Clin Ther 2008;30:587‐604.
Acknowledgments
We wish to thank Mami Nakayama, Miho Nakao-Kogure, Katsue Shiramizu, Miyuki Nishikata, and Makiko Kiyohiro (Kurume University) for their technical assistance. We also thank radiation technologists at Kurume University Hospital for their excellent technical assistance.
Disclosures
Akihiro Honda, Nobuhiro Tahara, Atsuko Tahara, Munehisa Bekki, Shoko Maeda-Ogata, Yoichi Sugiyama, Sachiyo Igata, Yuri Nishino, Takanori Matsui, Seiji Kurata, Toshi Abe, Sho-ichi Yamagishi, and Yoshihiro Fukumoto have nothing to disclose regarding the current study.
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Honda, A., Tahara, N., Tahara, A. et al. Effects of olmesartan and amlodipine on blood pressure, endothelial function, and vascular inflammation. J. Nucl. Cardiol. 30, 1613–1626 (2023). https://doi.org/10.1007/s12350-023-03200-y
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DOI: https://doi.org/10.1007/s12350-023-03200-y