Resistant hypertension (RH) is a multifactorial disease, frequently associated with obesity and characterized by blood pressure above goal (140/90 mm Hg) despite the concurrent use of ≥3 antihypertensive drugs of different classes. The mechanisms of obesity-related hypertension include, among others, aldosterone excess and inflammatory adipokines, which have demonstrated a significant role in the pathogenesis of metabolic syndrome and RH. This review aims to summarize recent studies on the role of the adipokines leptin, resistin, and adiponectin in the pathophysiology of RH and target-organ damage associated with this condition. The deregulation of adipokine levels has been associated with clinical characteristics frequently recognized in RH such as diabetes, hyperactivity of sympathetic and renin-angiotensin-aldosterone systems, and vascular and renal damage. Strategies to regulate adipokines may be promising for the management of RH and some clinical implications must be considered when managing controlled and uncontrolled patients with RH.1610754759Calhoun, D.A., Jones, D., Textor, S., Resistant hypertension: diagnosis, evaluation, and treatment. A scientific statement from the American Heart Association Professional Education Committee of the Council for High Blood Pressure Research (2008) Hypertension., 51, pp. 1403-1419Wang, Z.V., Scherer, P.E., Adiponectin, cardiovascular function, and hypertension (2008) Hypertension., 51, pp. 8-14Sutton-Tyrrell, K., Newman, A., Simonsick, E.M., Aortic stiffness is associated with visceral adiposity in older adults enrolled in the study of health, aging, and body composition (2001) Hypertension., 38, pp. 429-433Salles, G.F., Fiszman, R., Cardoso, C.R., Muxfeldt, E.S., Relation of left ventricular hypertrophy with systemic inflammation and endothelial damage in resistant hypertension (2007) Hypertension., 50, pp. 723-728Salles, G.F., Cardoso, C.R., Pereira, V.S., Prognostic significance of a reduced glomerular filtration rate and interaction with microalbuminuria in resistant hypertension: a cohort study (2011) J Hypertens., 29, pp. 2014-2023Kurukulasuriya, L.R., Stas, S., Lastra, G., Hypertension in obesity (2011) Med Clin North Am., 95, pp. 903-917Hall, J.E., The kidney, hypertension, and obesity (2003) Hypertension., 41, pp. 625-633Hall, J.E., Crook, E.D., Jones, D.W., Mechanisms of obesity-associated cardiovascular and renal disease (2002) Am J Med Sci., 324, pp. 127-137Hall, J.E., Mechanisms of abnormal renal sodium handling in obesity hypertension (1997) Am J Hypertens., 10, pp. 49S-55SVollenweider, P., Tappy, L., Randin, D., Differential effects of hyperinsulinemia and carbohydrate metabolism on sympathetic nerve activity and muscle blood flow in humans (1993) J Clin Invest., 92, pp. 147-154Julius, S., Valentini, M., Palatini, P., Overweight and hypertension: a 2-way street? (2000) Hypertension., 35, pp. 807-813Rahmouni, K., Morgan, D.A., Hypothalamic arcuate nucleus mediates the sympathetic and arterial pressure responses to leptin (2007) Hypertension., 49, pp. 647-652DiBona, G.F., Nervous kidney. Interaction between renal sympathetic nerves and the renin-angiotensin system in the control of renal function (2000) Hypertension., 36, pp. 1083-1088Bentley-Lewis, R., Adler, G.K., Perlstein, T., Body mass index predicts aldosterone production in normotensive adults on a high-salt diet (2007) J Clin Endocrinol Metab., 92, pp. 4472-4475Ehrhart-Bornstein, M., Arakelyan, K., Krug, A.W., Fat cells may be the obesity-hypertension link: human adipogenic factors stimulate aldosterone secretion from adrenocortical cells (2004) Endocr Res., 30, pp. 865-870Engeli, S., Bohnke, J., Gorzelniak, K., Weight loss and the renin-angiotensin-aldosterone system (2005) Hypertension., 45, pp. 356-362Messerli, F.H., Christie, B., DeCarvalho, J.G., Obesity and essential hypertension. Hemodynamics, intravascular volume, sodium excretion, and plasma renin activity (1981) Arch Intern Med., 141, pp. 81-85Strazzullo, P., Barba, G., Cappuccio, F.P., Altered renal sodium handling in men with abdominal adiposity: a link to hypertension (2001) J Hypertens., 19, pp. 2157-2164McCurley, A., Pires, P.W., Bender, S.B., Direct regulation of blood pressure by smooth muscle cell mineralocorticoid receptors (2012) Nat Med., 18, pp. 1429-1433Bender, S.B., McGraw, A.P., Jaffe, I.Z., Sowers, J.R., Mineralocorticoid receptor-mediated vascular insulin resistance: an early contributor to diabetes-related vascular disease? (2013) Diabetes., 62, pp. 313-319Silva, E.A., Flexa, F., Zanella, M.T., Impact of abdominal fat and insulin resistance on arterial hypertension in non-obese women (2009) Arq Bras Endocrinol Metabol., 53, pp. 340-343Yatabe, M.S., Yatabe, J., Yoneda, M., Salt sensitivity is associated with insulin resistance, sympathetic overactivity, and decreased suppression of circulating renin activity in lean patients with essential hypertension (2010) Am J Clin Nutr., 92, pp. 77-82Sowers, J.R., Whaley-Connell, A., Epstein, M., Narrative review: the emerging clinical implications of the role of aldosterone in the metabolic syndrome and resistant hypertension (2009) Ann Intern Med., 150, pp. 776-783Gaddam, K.K., Nishizaka, M.K., Pratt-Ubunama, M.N., Characterization of resistant hypertension: association between resistant hypertension, aldosterone, and persistent intravascular volume expansion (2008) Arch Intern Med., 168, pp. 1159-1164Bomback, A.S., Klemmer, P.J., The incidence and implications of aldosterone breakthrough (2007) Nat Clin Pract Nephrol., 3, pp. 486-492de Souza, F., Muxfeldt, E., Fiszman, R., Salles, G., Efficacy of spironolactone therapy in patients with true resistant hypertension (2010) Hypertension., 55, pp. 147-152da Silva, A.A., do Carmo, J., Dubinion, J., Hall, J.E., The role of the sympathetic nervous system in obesity-related hypertension (2009) Curr Hypertens Rep., 11, pp. 206-211Fang, C., Lei, J., Zhou, S.X., Association of higher resistin levels with inflammatory activation and endothelial dysfunction in patients with essential hypertension (2013) Chin Med J (Engl)., 126, pp. 646-649Guo, C., Ricchiuti, V., Lian, B.Q., Mineralocorticoid receptor blockade reverses obesity-related changes in expression of adiponectin, peroxisome proliferator-activated receptor-gamma, and proinflammatory adipokines (2008) Circulation., 117, pp. 2253-2261Reaven, G., Abbasi, F., McLaughlin, T., Obesity, insulin resistance, and cardiovascular disease (2004) Recent Prog Horm Res., 59, pp. 207-223Kershaw, E.E., Flier, J.S., Adipose tissue as an endocrine organ (2004) J Clin Endocrinol Metab., 89, pp. 2548-2556Zhang, Y., Proenca, R., Maffei, M., Positional cloning of the mouse obese gene and its human homologue (1994) Nature., 372, pp. 425-432Collins, S., Kuhn, C.M., Petro, A.E., Role of leptin in fat regulation (1996) Nature., 380, p. 677Martin, S.S., Qasim, A., Reilly, M.P., Leptin resistance: a possible interface of inflammation and metabolism in obesity-related cardiovascular disease (2008) J Am Coll Cardiol., 52, pp. 1201-1210Correia, M.L., Haynes, W.G., Rahmouni, K., The concept of selective leptin resistance: evidence from agouti yellow obese mice (2002) Diabetes., 51, pp. 439-442El-Haschimi, K., Pierroz, D.D., Hileman, S.M., Two defects contribute to hypothalamic leptin resistance in mice with diet-induced obesity (2000) J Clin Invest., 105, pp. 1827-1832Gruen, M.L., Hao, M., Piston, D.W., Hasty, A.H., Leptin requires canonical migratory signaling pathways for induction of monocyte and macrophage chemotaxis (2007) Am J Physiol Cell Physiol., 293, pp. C1481-C1488Northcott, J.M., Yeganeh, A., Taylor, C.G., Adipokines and the cardiovascular system: mechanisms mediating health and disease (2012) Can J Physiol Pharmacol., 90, pp. 1029-1059Patel, L., Buckels, A.C., Kinghorn, I.J., Resistin is expressed in human macrophages and directly regulated by PPAR gamma activators (2003) Biochem Biophys Res Commun., 300, pp. 472-476McTernan, P.G., Fisher, F.M., Valsamakis, G., Resistin and type 2 diabetes: regulation of resistin expression by insulin and rosiglitazone and the effects of recombinant resistin on lipid and glucose metabolism in human differentiated adipocytes (2003) J Clin Endocrinol Metab., 88, pp. 6098-6106Yaturu, S., Daberry, R.P., Rains, J., Jain, S., Resistin and adiponectin levels in subjects with coronary artery disease and type 2 diabetes (2006) Cytokine., 34, pp. 219-223Iacobellis, G., Petramala, L., Cotesta, D., Adipokines and cardiometabolic profile in primary hyperaldosteronism (2010) J Clin Endocrinol Metab., 95, pp. 2391-2398Vaidya, A., Pojoga, L., Underwood, P.C., The association of plasma resistin with dietary sodium manipulation, the renin-angiotensin-aldosterone system, and 25-hydroxyvitamin D3 in human hypertension (2011) Clin Endocrinol (Oxf)., 74, pp. 294-299Bokarewa, M., Nagaev, I., Dahlberg, L., Resistin, an adipokine with potent proinflammatory properties (2005) J Immunol., 174, pp. 5789-5795Calabro, P., Samudio, I., Willerson, J.T., Yeh, E.T., Resistin promotes smooth muscle cell proliferation through activation of extracellular signal-regulated kinase 1/2 and phosphatidylinositol 3-kinase pathways (2004) Circulation., 110, pp. 3335-3340Cnop, M., Havel, P.J., Utzschneider, K.M., Relationship of adiponectin to body fat distribution, insulin sensitivity and plasma lipoproteins: evidence for independent roles of age and sex (2003) Diabetologia., 46, pp. 459-469Fasshauer, M., Kralisch, S., Klier, M., Adiponectin gene expression and secretion is inhibited by interleukin-6 in 3T3-L1 adipocytes (2003) Biochem Biophys Res Commun., 301, pp. 1045-1050Ouchi, N., Kihara, S., Arita, Y., Adiponectin, an adipocyte-derived plasma protein, inhibits endothelial NF-kappaB signaling through a cAMP-dependent pathway (2000) Circulation., 102, pp. 1296-1301Koenig, W., Khuseyinova, N., Baumert, J., Serum concentrations of adiponectin and risk of type 2 diabetes mellitus and coronary heart disease in apparently healthy middle-aged men: results from the 18-year follow-up of a large cohort from southern Germany (2006) J Am Coll Cardiol., 48, pp. 1369-1377Ouchi, N., Ohishi, M., Kihara, S., Association of hypoadiponectinemia with impaired vasoreactivity (2003) Hypertension., 42, pp. 231-234Hong, S.J., Park, C.G., Seo, H.S., Associations among plasma adiponectin, hypertension, left ventricular diastolic function and left ventricular mass index (2004) Blood Press., 13, pp. 236-242Youn, J.C., Kim, C., Park, S., Adiponectin and progression of arterial stiffness in hypertensive patients (2013) Int J Cardiol., 163, pp. 316-319Iwashima, Y., Katsuya, T., Ishikawa, K., Hypoadiponectinemia is an independent risk factor for hypertension (2004) Hypertension., 43, pp. 1318-1323Chow, W.S., Cheung, B.M., Tso, A.W., Hypoadiponectinemia as a predictor for the development of hypertension: a 5-year prospective study (2007) Hypertension., 49, pp. 1455-1461Li, P., Zhang, X.N., Pan, C.M., Aldosterone perturbs adiponectin and PAI-1 expression and secretion in 3T3-L1 adipocytes (2011) Horm Metab Res., 43, pp. 464-469Koh, K.K., Quon, M.J., Lee, Y., Additive beneficial cardiovascular and metabolic effects of combination therapy with ramipril and candesartan in hypertensive patients (2007) Eur Heart J., 28, pp. 1440-1447Fontana, V., de Faria, A.P., Oliveira-Paula, G.H., Effects of angiotensin-converting enzyme inhibition on leptin and adiponectin levels in essential hypertension (2014) Basic Clin Pharmacol Toxicol., 114, pp. 472-475Furuhashi, M., Ura, N., Higashiura, K., Blockade of the renin-angiotensin system increases adiponectin concentrations in patients with essential hypertension (2003) Hypertension., 42, pp. 76-81Fallo, F., Della Mea, P., Sonino, N., Adiponectin and insulin sensitivity in primary aldosteronism (2007) Am J Hypertens, 20, pp. 855-861Cushman, W.C., Ford, C.E., Cutler, J.A., Success and predictors of blood pressure control in diverse North American settings: the antihypertensive and lipid-lowering treatment to prevent heart attack trial (ALLHAT) (2002) J Clin Hypertens (Greenwich)., 4, pp. 393-404Boer-Martins, L., Figueiredo, V.N., Demacq, C., Relationship of autonomic imbalance and circadian disruption with obesity and type 2 diabetes in resistant hypertensive patients (2011) Cardiovasc Diabetol., 10, p. 24Boer-Martins, L., Figueiredo, V.N., Demacq, C., Leptin and aldosterone in sympathetic activity in resistant hypertension with or without type 2 diabetes (2012) Arq Bras Cardiol., 99, pp. 642-648Williams, J.S., Evolving research in nongenomic actions of aldosterone (2013) Curr Opin Endocrinol Diabetes Obes., 20, pp. 198-203Grossmann, C., Krug, A.W., Freudinger, R., Aldosterone-induced EGFR expression: interaction between the human mineralocorticoid receptor and the human EGFR promoter (2007) Am J Physiol Endocrinol Metab., 292, pp. E1790-E1800Martins, L.C., Figueiredo, V.N., Quinaglia, T., Characteristics of resistant hypertension: ageing, body mass index, hyperaldosteronism, cardiac hypertrophy and vascular stiffness (2011) J Hum Hypertens., 25, pp. 532-538de Haro Moraes, C., Figueiredo, V.N., de Faria, A.P., High-circulating leptin levels are associated with increased blood pressure in uncontrolled resistant hypertension (2013) J Hum Hypertens., 27, pp. 225-230de Faria, A.P., Demacq, C., Figueiredo, V.N., Hypoadiponectinemia and aldosterone excess are associated with lack of blood pressure control in subjects with resistant hypertension (2013) Hypertens Res., 36, pp. 1067-1072Sabbatini, A.R., Faria, A.P., Barbaro, N.R., Deregulation of adipokines related to target organ damage on resistant hypertension (2014) J Hum Hypertens., 28, pp. 388-392Esposito, K., Pontillo, A., Di Palo, C., Effect of weight loss and lifestyle changes on vascular inflammatory markers in obese women: a randomized trial (2003) JAMA., 289, pp. 1799-1804Pimenta, E., Gaddam, K.K., Oparil, S., Effects of dietary sodium reduction on blood pressure in subjects with resistant hypertension: results from a randomized trial (2009) Hypertension., 54, pp. 475-481Baudrand, R., Lian, C.G., Lian, B.Q., Long-term dietary sodium restriction increases adiponectin expression and ameliorates the proinflammatory adipokine profile in obesity (2014) Nutr Metab Cardiovasc Dis., 24, pp. 34-41Hollenberg, N.K., Williams, G.H., Nonmodulation and essential hypertension (2006) Curr Hypertens Rep., 8, pp. 127-131Nedogoda, S.V., Ledyaeva, A.A., Chumachok, E.V., Randomized trial of perindopril, enalapril, losartan and telmisartan in overweight or obese patients with hypertension (2013) Clin Drug Investig., 33, pp. 553-561Combs, T.P., Wagner, J.A., Berger, J., Induction of adipocyte complement-related protein of 30 kilodaltons by PPARgamma agonists: a potential mechanism of insulin sensitization (2002) Endocrinology., 143, pp. 998-1007Araki, K., Masaki, T., Katsuragi, I., Effects of pravastatin on obesity, diabetes, and adiponectin in diet-induced obese mice (2008) Obesity (Silver Spring)., 16, pp. 2068-2073Pierdomenico, S.D., Lapenna, D., Bucci, A., Cardiovascular outcome in treated hypertensive patients with responder, masked, false resistant, and true resistant hypertension (2005) Am J Hypertens., 18, pp. 1422-1428