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Modulation of Vascular Reactivity by Perivascular Adipose Tissue (PVAT)

  • Hypertension and Obesity (E Reisin, Section Editor)
  • Published:
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Abstract

Purpose of Review

In this review, we discuss the role of perivascular adipose tissue (PVAT) in the modulation of vascular contractility and arterial pressure, focusing on the role of the renin-angiotensin-aldosterone system and oxidative stress/inflammation.

Recent Findings

PVAT possesses a relevant endocrine-paracrine activity, which may be altered in several pathophysiological and clinical conditions. During the last two decades, it has been shown that PVAT may modulate vascular reactivity. It has also been previously demonstrated that inflammation in adipose tissue may be implicated in vascular dysfunction. In particular, adipocytes secrete a number of adipokines with various functions, as well as several vasoactive factors, together with components of the renin-angiotensin system which may act at local or at systemic level. It has been shown that the anti-contractile effect of PVAT is lost in obesity, probably as a consequence of the development of adipocyte hypertrophy, inflammation, and oxidative stress.

Summary

Adipose tissue dysfunction is interrelated with inflammation and oxidative stress, thus contributing to endothelial dysfunction observed in several pathological and clinical conditions such as obesity and hypertension. Decreased local adiponectin level, macrophage recruitment and infiltration, and activation of renin-angiotensin-aldosterone system could play an important role in this regard.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Galic S, Oakhill JS, Steinberg GR. Adipose tissue as an endocrine organ. Mol Cell Endocrinol. 201025;316(2):129–39.

  2. •• Soltis EE, Cassis LA. Influence of adipose tissue on rat aortic smooth muscle responsiveness. Clin Exp Hypertens A. 1991;13(2):277–96. First demonstration that PVAT might be important for vascular regulation.

    PubMed  CAS  Google Scholar 

  3. Lohn M, Dubrovska G, Lauterbach B, Luft FC, Gollasch M, Sharma AM. Periadventitial fat releases a vascular relaxing factor. FASEB J. 2002;16(9):1057–63.

    Article  PubMed  Google Scholar 

  4. Dubrovska G, Verlohren S, Luft FC, Gollasch M. Mechanisms of ADRF release from rat aortic adventitial adipose tissue. Am J Physiol Heart Circ Physiol. 2003;286(3):H1107–13.

    Article  PubMed  Google Scholar 

  5. Archer SL, Gragasin FS, Wu X, Wang S, McMurtry S, Kim DH, et al. Endothelium-derived hyperpolarizing factor in human internal mammary artery is 11,12-epoxyeicosatrienoic acid and causes relaxation by activating smooth muscle BK (Ca) channels. Circulation. 2003;107(5):769–76.

    Article  PubMed  CAS  Google Scholar 

  6. Verlohren S, Dubrovska G, Tsang S-Y, EEssin K, Luft FC, Huang Y, et al. Visceral periadventitial adipose tissue regulates arterial tone of mesenteric arteries [comment]. Hypertension. 2004;44(3):271–6.

    Article  PubMed  CAS  Google Scholar 

  7. Gao Y-J, Zeng Z-H, Teoh K, Sharma AM, Abouzahr L, Cybulsky I, et al. Perivascular adipose tissue modulates vascular function in the human internal thoracic artery. J Thorac Cardiovas Surg. 2005;130(4):1130–6.

    Article  Google Scholar 

  8. Gálvez B, de Castro J, Herold D, Dubrovska G, Arribas S, González MC, et al. Perivascular adipose tissue and mesenteric vascular function in spontaneously hypertensive rats. Arterioscler Thromb Vasc Biol. 2006;26(6):1297–302.

    Article  PubMed  CAS  Google Scholar 

  9. Gao YJ, Lu C, Su LY, Sharma AM, Lee RMKW. Modulation of vascular function by perivascular adipose tissue: the role of endothelium and hydrogen peroxide. [comment]. Br J Pharmacol. 2007;151(3):323–31.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  10. Malinowski M, Deja MA, Gołba KS, Roleder T, Biernat J, Woś S. Perivascular tissue of internal thoracic artery releases potent nitric oxide and prostacyclin-independent anticontractile factor. Eur J Cardiothorac Surg. 2008;33(2):225–31.

    Article  PubMed  Google Scholar 

  11. •• Greenstein AS, Khavandi K, Withers SB, Sonoyama K, Clancy O, Jeziorska M, et al. Local inflammation and hypoxia abolish the protective anticontractile properties of perivascular fat in obese patients. Circulation. 2009;119(12):1661–70. This is the first demonstration of anticontractile effect of perivascular adipose tissue in obese patients.

    Article  PubMed  CAS  Google Scholar 

  12. Lee RM, Ding L, Lu C, Su LY, Gao YJ. Alteration of perivascular adipose tissue function in angiotensin II-induced hypertension. Can J Physiol Pharmacol. 2009;87(11):944–53.

    Article  PubMed  CAS  Google Scholar 

  13. Lee RMKW, Lu C, Su LY, Gao YJ. Endothelium-dependent relaxation factor released by perivascular adipose tissue. J Hypertens. 2009;27(4):782–90.

    Article  PubMed  CAS  Google Scholar 

  14. Lu C, Zhao AX, Gao YJ, Lee RM. Modulation of vein function by perivascular adipose tissue. Eur J Pharmacol. 2011;657(1–3):111–6.

    Article  PubMed  CAS  Google Scholar 

  15. Baker AR, Silva NF, Quinn DW, Harte AL, Pagano D, Bonser RS, et al. Human epicardial adipose tissue expresses a pathogenic profile of adipocytokines in patients with cardiovascular disease. Cardiovasc Diabetol. 2006;5:1.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  16. Quehenberger P, Exner M, Sunder-Plassmann R, Ruzicka K, Bieglmayer C, Endler G, et al. Leptin induces endothelin-1 in endothelial cells in vitro. Circ Res. 2002;90(6):711–8.

    Article  PubMed  CAS  Google Scholar 

  17. Korda M, Kubant R, Patton S, Malinski T. Leptin-induced endothelial dysfunction in obesity. Am J Physiol Heart Circ Physiol. 2008;295(4):H1514–21.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  18. Ketonen J, Shi J, Martonen E, Mervaala E. Periadventitial adipose tissue promotes endothelial dysfunction via oxidative stress in diet-induced obese C57BI/6 mice. Circ J. 2010;74(7):1479–87.

    Article  PubMed  CAS  Google Scholar 

  19. Yamamoto K, Kiyohara T, Murayama Y, Kihara S, Okamoto Y, Funahashi T, et al. Production of adiponectin, an anti-inflammatory protein, in mesenteric adipose tissue in Crohn’s disease. Gut. 2005;54(6):789–96.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  20. Trujillo ME, Scherer PE. Adiponectin—journey from an adipocyte secretory protein to biomarker of the metabolic syndrome. J Intern Med. 2005;257(2):167–75.

    Article  PubMed  CAS  Google Scholar 

  21. Chow W-S, Cheung BMY, Tso AWK, Xu A, Wat NMS, Fong CHY, et al. Hypoadiponectinemia as a predictor for the development of hypertension: a 5-year prospective study. [comment]. Hypertension. 2007;49(6):1455–61.

    Article  PubMed  CAS  Google Scholar 

  22. Li H-Y, Chiu Y-F, Hwu C-M, Sheu WH-H, Hung Y-J, Fujimoto W, et al. The negative correlation between plasma adiponectin and blood pressure depends on obesity: a family-based association study in SAPPHIRe. [comment]. Am J Hypertens. 2008;21(4):471–6.

    Article  PubMed  CAS  Google Scholar 

  23. • Iwashima Y, Katsuya T, Ishikawa K, Ouchi N, Ohishi M, Sugimoto K, et al. Hypoadiponectinemia is an independent risk factor for hypertension. Hypertension. 2004;43(6):1318–23. This is one of the first study that describes the several protective properties of adiponectin against hypertension.

    Article  PubMed  CAS  Google Scholar 

  24. Yamauchi T, Kamon J, Waki H, Imai Y, Shimozawa N, Hioki K, et al. Globular adiponectin protected ob/ob mice from diabetes and ApoE-deficient mice from atherosclerosis. J Biol Chem. 2003;278(4):2461–8.

    Article  PubMed  CAS  Google Scholar 

  25. Yamauchi T, Kamon J, Waki H, Terauchi Y, Kubota N, Hara K, et al. The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. [comment]. Nat Med. 2001;7(8):941–6.

    Article  PubMed  CAS  Google Scholar 

  26. Deng G, Long Y, Yu YR, Li MR. Adiponectin directly improves endothelial dysfunction in obese rats through the AMPK-eNOS pathway. Int J Obes. 2010;34:165–71.

    Article  CAS  Google Scholar 

  27. Luo N, Liu J, Chung BH, Yang Q, Klein RL, Garvey WT, et al. Macrophage adiponectin expression improves insulin sensitivity and protects against inflammation and atherosclerosis. Diabetes. 2010;59(4):791–9.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  28. Li FY, Cheng KK, Lam KS, Vanhoutte PM, Xu A. Cross-talk between adipose tissue and vasculature: role of adiponectin. Acta Physiol (Oxf). 2011;203(1):167–80.

    Article  CAS  Google Scholar 

  29. Cao Y, Tao L, Yuan YX, Jiao XY, Lau WB, Wang YJ, et al. Endothelial dysfunction in adiponectin deficiency and its mechanisms involved. J Mol Cell Cardiol. 2009;46(3):413–9.

    Article  PubMed  CAS  Google Scholar 

  30. Sowers JR. Endocrine functions of adipose tissue: focus on adiponectin. Clin Cornerstone. 2008;9:32–38, discussion 39–40.

    Article  PubMed  Google Scholar 

  31. Iacobellis G, Pistilli D, Gucciardo M, Leonetti F, Miraldi F, Brancaccio G, et al. Adiponectin expression in human epicardial adipose tissue in vivo is lower in patients with coronary artery disease. Cytokine. 2005;29(6):251–5.

    PubMed  CAS  Google Scholar 

  32. An SJ, Boyd R, Wang Y, Qiu X, Wang HD. Endothelin-1 expression in vascular adventitial fibroblasts. Am J Physiol Heart Circ Physiol. 2006;290:H700–8.

    Article  PubMed  CAS  Google Scholar 

  33. Ahima RS, Flier JS. Adipose tissue as an endocrine organ. Trends in Endocrinology & Metabolism. 2000;11(9):237–2.

    Google Scholar 

  34. Berg AH, Scherer PE. Adipose tissue, inflammation, and cardiovascular disease. Circ Res. 2005;96:939–49.

    Article  PubMed  CAS  Google Scholar 

  35. Wellen KE, Hotamisligil GS. Inflammation, stress, and diabetes. J Clin Invest. 2005;115:1111–9.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  36. Despres JP, Lemieux I. Abdominal obesity and metabolic syndrome. Nature. 2006;444:881–7.

    Article  PubMed  CAS  Google Scholar 

  37. Lazar MA. How obesity causes diabetes: not a tall tale. Science. 2005;307:373–5.

    Article  PubMed  CAS  Google Scholar 

  38. • Engeli S, Gorzelniak K, Kreutz R, Runkel N, Distler A, Sharma AM. Co-expression of renin-angiotensin system genes in human adipose tissue. Journal of Hypertension. 1999;17:555–60. The study describes the role of the renin-angiotensin system in human adipose tissue.

    Article  PubMed  CAS  Google Scholar 

  39. Gàlvez-Prieto B, Bolbrinker J, Stucchi P, de Las Heras AI, Merino B, Arribas S, et al. Comparative expression analysis of the renin-angiotensin system components between white and brown perivascular adipose tissue. J Endocrinol. 2008;197:55–64.

    Article  PubMed  CAS  Google Scholar 

  40. Goossens GH, Jocken JW, Blaak EE, Schiffers PM, Saris WH, van Baak MA. Endocrine role of the renin-angiotensin system in human adipose tissue and muscle: effect of beta-adrenergic stimulation. Hypertension. 2007;49(3):542–7.

    Article  PubMed  CAS  Google Scholar 

  41. • Cassis LA, Police SB, Yiannikouris F, Thatcher SE. Local adipose tissue renin-angiotensin system. Curr Hypertens Rep. 2008;10(2):93–8. This study is a review of the important role of adipose tissue renin-angiotensin system.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  42. Campbell DJ, Habener JF. Cellular localization of AGT gene expression in brown adipose tissue and mesentery: quantification of messenger ribonucleic acid abundance using hybridization in situ. Endocrinology. 1987;121:1616–26.

    Article  PubMed  CAS  Google Scholar 

  43. Cassis LA, Lynch KR, Peach MJ. Localization of angiotensinogen messenger RNA in rat aorta. Circ Res. 1988;62:1259–62.

    Article  PubMed  CAS  Google Scholar 

  44. Shiling P, Mallow H, Trindl A, Loffler G. Evidence for a local renin angiotensin system in primary cultured human preadipocytes. Internal Journal Obes Relat Metab Disord. 1999;23:336–41.

    Article  CAS  Google Scholar 

  45. Saye J, Linch KR, Peach MJ. Changes in angiotensinogen messenger RNA in differentiating 3T3-F442A adipocytes. Hypertension. 1990;15:867–71.

    Article  PubMed  CAS  Google Scholar 

  46. Hainault I, Nebout G, Ardouin BB, Quignard-Boulangé A. Developmental changes in AGT expression and its secretion in the Zucker rat: adipose tissue-specific effect of FA genotype. Int J Obes Relat Metab Disord. 1998;22(suppl 3):S103. Abstract

    Google Scholar 

  47. Giacchetti G, Faloia E, Sardu C, Mariniello B, Garrapa GGM, Gatti C, et al. Different gene expression of the RAS in human subcutaneous and visceral adipose tissue. Int J Obes Relat Metab Disord. 1999;23(suppl 5):S71. Dent Abstr

    Google Scholar 

  48. Phillips MI, Speakman EA, Kimura B. Levels of angiotensin and molecular biology of the tissue renin angiotensin systems. Regul Pept. 1993;43:1–20.

    Article  PubMed  CAS  Google Scholar 

  49. Shenoy U, Cassis L. Characterization of renin activity in brown adipose tissue. Am J Phys. 1997;272:C989–99.

    Article  CAS  Google Scholar 

  50. Kupiers I, van der Harst P, Navis G, et al. Nuclear hormone receptors as regulators of the renin-angiotensin-aldosterone system. Hypertension. 2008;51:1442–8.

    Article  CAS  Google Scholar 

  51. Archard V, Boullu-Ciocca S, Desbriere R, Nguyen G, Grino M. Renin receptor expression in human adipose tissue. Am J Physiol Reg Int Comp Physiol. 2007;292:274–82.

    Article  CAS  Google Scholar 

  52. Touyz RM, Schiffrin EL. Signal transduction mechanisms mediating the physiological and pathophysiological actions of angiotensin II in vascular smooth muscle cells. Pharmacol Rev. 2000;52:639–72.

    PubMed  CAS  Google Scholar 

  53. Schling P, Mallow H, Trindl A, Löffler G. Evidence for a local renin angiotensin system in primary cultured human preadipocytes. Int J Obes Relat Metab Disord. 1999;23(4):336–41.

    Article  PubMed  CAS  Google Scholar 

  54. Sharma AM, Janke J, Gorzelniak K, Engeli S, Luft FC. Angiotensin blockade prevents type 2 diabetes by formation of fat cells. Hypertension. 2002;40:609–11.

    Article  PubMed  CAS  Google Scholar 

  55. Matsushita K, Wu Y, Okamoto Y, Pratt RE, Dzau VJ. Local renin-angiotensin expression regulates human mesenchymal stem cell differentiation to adipocytes. Hypertension. 2006;48:1095–102.

    Article  PubMed  CAS  Google Scholar 

  56. Jones BH, Standridge MK, Moustaid N. Angiotensin II increases lipogenesis in 3T3-L1 and human adipose cells. Endocrinology. 1997;138(4):1512–9.

    Article  PubMed  CAS  Google Scholar 

  57. Furuhashi M, Ura N, Higashiura K, Murakami H, Tanaka M, Moniwa N, et al. Blockade of the renin–angiotensin system increases adiponectin concentrations in patients with essential hypertension. Hypertension. 2003;42:76–81.

    Article  PubMed  CAS  Google Scholar 

  58. Lee MH, Song HK, Ko GJ, Kang YS, Han SY, Han KH, et al. Angiotensin receptor blockers improve insulin resistance in type 2 diabetic rats by modulating adipose tissue. Kidney Int. 2008;74:890–900.

    Article  PubMed  CAS  Google Scholar 

  59. Rinaldi B, Di Filippo C, Capuano A, Donniacuo M, Sodano L, Ferraraccio F, et al. Adiponectin elevation by telmisartan ameliorates ischaemic myocardium in Zucker diabetic fatty rats with metabolic syndrome. Diabetes Obes Metab. 2012;14(4):320–8.

    Article  PubMed  CAS  Google Scholar 

  60. Nakamura T, Kawachi K, Saito Y, Saito T, Morishita K, Hoshino J, et al. Effects of ARB or ACE-inhibitor administration on plasma levels of aldosterone and adiponectin in hypertension. Int Heart J. 2009;50:501–12.

    Article  PubMed  CAS  Google Scholar 

  61. Ran J, Hirano T, Fukui T, Saito K, Kageyama H, Okada K, et al. Angiotensin II infusion decreases plasma adiponectin level via its type 1 receptor in rats: an implication for hypertension-related insulin resistance. Metabolism. 2006;55:478–88.

    Article  PubMed  CAS  Google Scholar 

  62. Guo B, Li Y, Han R, Zhou H, Wang M. Angiotensin II upregulation of cardiomyocyte adiponectin production is nitric oxide/cyclic GMP dependent. Am J Med Sci. 2011;341(5):350–5.

    Article  PubMed  Google Scholar 

  63. Onat A. Metabolic syndrome: nature, therapeutic solutions and options. Expert Opin Pharmacother. 2011;12(12):1887–900.

    Article  PubMed  CAS  Google Scholar 

  64. Okada S, Kozuka C, Masuzaki H, Yasue S, Ishii-Yonemoto T, Tanaka T, et al. Adipose tissue-specific dysregulation of angiotensinogen by oxidative stress in obesity. Metabolism Journal. 2010;59(9):1241–51.

    Article  CAS  Google Scholar 

  65. Farquharson CA, Struthers AD. Aldosterone induces acute endothelial dysfunction in vivo in humans: evidence for an aldosterone-induced vasculopathy. Clin Sci (Lond). 2002;103(4):425–31.

    Article  CAS  Google Scholar 

  66. Sun Y, Zhang J, Lu L, Chen SS, Quinn MT, Weber KT. Aldosterone-induced inflammation in the rat heart: role of oxidative stress. Am J Pathol. 2002;161(5):1773–81.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  67. Hirata A, Maeda N, Hiuge A, Hibuse T, Fujita K, Okada T, et al. Blockade of mineralcorticoid receptor reverses adipocyte dysfunction and insulin resistance in obese mice. Cardiovasc Res. 2009;84:164–72.

    Article  PubMed  CAS  Google Scholar 

  68. Flynn C, Bakris GL. Interaction between adiponectin and aldosterone. Cardiorenal Med. 2011;1(2):96–101.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  69. Lemarié CA, Paradis P, Schiffrin EL. New insights on signaling cascades induced by cross-talk between angiotensin II and aldosterone. J Mol Med. 2008;86(6):673–8.

    Article  PubMed  CAS  Google Scholar 

  70. Lu C, Su LY, Lee RM, Gao YJ. Mechanisms for perivascular adipose tissue-mediated potentiation of vascular contraction to perivascular neuronal stimulation: the role of adipocyte-derived angiotensin II. Eur J Pharmacol. 2010;634(1–3):107–12.

    Article  PubMed  CAS  Google Scholar 

  71. Lu C, Su LY, Lee RM, Gao YJ. Alterations in perivascular adipose tissue structure and function in hypertension. Eur J Pharmacol. 2011;656(1–3):68–73.

    Article  PubMed  CAS  Google Scholar 

  72. •• Withers SB, Agabiti Rosei C, Livingstone DM, Little MC, Aslam R, Malik RA, et al. Macrophage activation is responsible for loss of anticontractile function in inflamed perivascular fat. Artherioscler Thromb, Vascular, Biol. 2011;31(4):908–13. This study demonstrates the involvement of macrophage activation in loss of anticontractile function of perivascular adipose tissue.

    Article  CAS  Google Scholar 

  73. • Rosei CA, Withers SB, Belcaid L, De Ciuceis C, Rizzoni D, Heagerty AM. Blockade of the renin-angiotensin system in small arteries and anticontractile function of perivascular adipose tissue. J Hypertens. 2015;33(5):1039–45. https://doi.org/10.1097/HJH. This is the first demonstration of restore anticontractile effect of perivascular fat with blockade of the renin-angiotensin system in small arteries

    Article  PubMed  CAS  Google Scholar 

  74. • Huang Cao ZF, Stoffel E, Cohen P. Role of perivascular adipose tissue in vascular physiology and pathology. Hypertension. 2017;69:770–7. This is a recent overview of the role of perivascular adipose tissue in vascular structure and reactivity.

    Article  PubMed  CAS  Google Scholar 

  75. Cancello R, Henegar C, Viguerie N, Taleb S, Poitou C, Rouault C, et al. Reduction of macrophage infiltration and chemoattractant gene expression changes in white adipose tissue of morbidly obese subjects after surgery-induced weight loss. Diabetes. 2005;54(8):2277–86.

    Article  PubMed  CAS  Google Scholar 

  76. Chen B, Lam KSL, Wang Y, Wu D, Larn MC, Shen J, et al. Hypoxia dysregulates the production of adiponectin and plasminogen activator inhibitor-1 independent of reactive oxygen species in adipocytes. Biochem Biophys Res Commun. 2006;341(2):549–56.

    Article  PubMed  CAS  Google Scholar 

  77. Patten DA, Lafleur VN, Robitaille GA, Chan DA, Giaccia AJ, Richard DE. Hypoxia-inducible factor-1 activation in nonhypoxic conditions: the essential role of mitochondrial-derived reactive oxygen species. Mol Biol Cell. 2010;21(18):3247–57.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  78. Pagé EL, Robitaille GA, Pouysségur J, Richard DE. Induction of hypoxia-inducible factor-1α by transcriptional and translational mechanisms. J Biol Chem. 2002;277(50):48403–9.

    Article  PubMed  Google Scholar 

  79. • Schnabel R, Larson MG, Dupuis J, Lunetta KL, Lipinska I, Meigs JB, et al. Relations of inflammatory biomarkers and common genetic variants with arterial stiffness and wave reflection. Hypertension. 2008;51(6):1651–7. This study shows that inflammation and oxidative stress are interrelated and associated with adipose tissue dysfunction and they could contribute to arterial stiffness and hypertension.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  80. Chae CU, Lee RT, Rifai N, Ridker PM. Blood pressure and inflammation in apparently healthy men. Hypertension. 2001;38(3):399–403.

    Article  PubMed  CAS  Google Scholar 

  81. Furukawa S, Fujita T, Shimabukuro M, Iwaki M, Yamada Y, Nakajima Y, et al. Increased oxidative stress in obesity and its impact on metabolic syndrome. J Clin Invest. 2004;114(12):1752–61.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  82. Kawanami D, Maemura K, Takeda N, Harada T, Nojiri T, Imai Y, et al. Direct reciprocal effects of resistin and adiponectin on vascular endothelial cells: a new insight into adipocytokine-endothelial cell interactions. Biochem Biophys Res Commun. 2004;314(2):415–9.

    Article  PubMed  CAS  Google Scholar 

  83. • FM L, Withers SB, Yao Z, Werner ME, Edwards G, Weston AH, et al. Perivascular adipose tissue-derived adiponectin activates BK(Ca) channels to induce anticontractile responses. Am J Physiol Heart Circ Physiol. 2013;(6):304, H786–H395. This study is the first demonstration that the mechanism underlies the anticontractile effect of perivascular adipose tissue involves the activation of BK(Ca) channels.

  84. Weston AH, Egner I, Dong Y, Porter EL, Heagerty AM, Edwards G. Stimulated release of a hyperpolarizing factor (ADHF) from mesenteric artery perivascular adipose tissue: involvement of myocyte BKCa channels and adiponectin. Br J Pharmacol. 2013;169(7):1500–9.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  85. • Withers SB, Simpson L, Fattah S, Werner ME, Heagerty AM. cGMP-dependent protein kinase (PKG) mediates the anticontractile capacity of perivascular adipose tissue. Cardiovasc Res. 2014;101(1):130–7. This study shows the role of cGMP-dependent protein kinase (PKG) as a principal mediators of perivascular adipose tissue activity.

    Article  PubMed  CAS  Google Scholar 

  86. Agabiti-Rosei C, De Ciuceis C, Rossini C, Porteri E, Rodella LF, Withers SB, et al. Anticontractile activity of perivascular fat in obese mice and the effect of long-term treatment with melatonin. J Hypertens. 2014;32(6):1264–74.

    Article  PubMed  CAS  Google Scholar 

  87. Bonnefont-Rousselot D, Collin F, Jore D, Gardès-Albert M. Reaction mechanism of melatonin oxidation by reactive oxygen species in vitro. J Pineal Res. 2011;50(3):328–35.

    Article  PubMed  CAS  Google Scholar 

  88. Rezzani R, Porteri E, De Ciuceis C, Bonomini F, Rodella LF, Paiardi S, et al. Effects of melatonin and pycnogenol on small artery structure and function in spontaneously hypertensive rats. Hypertension. 2010;55(6):1373–80.

    Article  PubMed  CAS  Google Scholar 

  89. Koziróg M, Poliwczak AR, Duchnowicz P, Koter-Michalak M, Sikora J, Broncel M. Melatonin treatment improves blood pressure, lipid profile, and parameters of oxidative stress in patients with metabolic syndrome. J Pineal Res. 2011;50(3):261–6.

    Article  PubMed  CAS  Google Scholar 

  90. Ríos-Lugo MJ, Cano P, Jiménez-Ortega V, Fernández-Mateos MP, Scacchi PA, Cardinali DP, et al. Melatonin effect on plasma adiponectin, leptin, insulin, glucose, triglycerides and cholesterol in normal and high fat-fed rats. J Pineal Res. 2010;49(4):342–8.

    Article  PubMed  CAS  Google Scholar 

  91. • Tan DX, Manchester LC, Fuentes-Broto L, Paredes SD, Reiter RJ. Significance and application of melatonin in the regulation of brown adipose tissue metabolism: relation to human obesity. Obes Rev. 2011;12(3):167–88. This study describes melatonin function in brown adipose tissue metabolism suggesting a potential target for treatment of obesity in humans.

    Article  PubMed  CAS  Google Scholar 

  92. Takeda T. Senescence-accelerated mouse (SAM): a biogerontological resource in aging research. Neurobiol Aging. 1999;20(2):105–10.

    Article  PubMed  CAS  Google Scholar 

  93. Butterfield DA, Poon HF. The senescence-accelerated prone mouse (SAMP8): a model of age-related cognitive decline with relevance to alterations of the gene expression and protein abnormalities in Alzheimer’s disease. Exp Gerontol. 2005;40(10):774–83.

    Article  PubMed  CAS  Google Scholar 

  94. Agabiti-Rosei C, Favero G, De Ciuceis C, Rossini C, Porteri E, Rodella LF, et al. Effect of long-term treatment with melatonin on vascular markers of oxidative stress/inflammation and on the anticontractile activity of perivascular fat in aging mice. Hypertens Res. 2017;40(1):41–50.

    Article  PubMed  CAS  Google Scholar 

  95. Narkiewicz K. Diagnosis and management of hypertension in obesity. Obes Rev. 2006;7(2):155–62.

    Article  PubMed  CAS  Google Scholar 

  96. Kotchen TA. Obesity-related hypertension: epidemiology, pathophysiology, and clinical management. Am J Hypertens. 2010;23(11):1170–8.

    Article  PubMed  CAS  Google Scholar 

  97. Mancia G, De Backer G, Dominiczak A, Cifkova R, Fagard R, Germano G, et al. Guidelines for the management of arterial hypertension: the task force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Eur Heart J. 2007;28(12):1462–536.

    PubMed  Google Scholar 

  98. Guo Z, Zheng C, Qin Z, Wei P. Effect of telmisartan on the expression of cardiac adiponectin and its receptor 1 in type 2 diabetic rats. J Pharm Pharmacol. 2011;63(1):87–94.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Medicine, Manchester University, Manchester, UK

    Claudia Agabiti-Rosei, Sarah Withers, Adam Greenstein & Anthony M. Heagerty

  2. Clinica Medica, Department of Medical and Surgical Sciences, University of Brescia, c/o 2a Medicina Spedali Civili di Brescia, Piazza Spedali Civili 1, 25100, Brescia, Italy

    Claudia Agabiti-Rosei, Anna Paini, Carolina De Ciuceis & Damiano Rizzoni

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  1. Claudia Agabiti-Rosei
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Correspondence to Claudia Agabiti-Rosei.

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This article is part of the Topical Collection on Hypertension and Obesity

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Agabiti-Rosei, C., Paini, A., De Ciuceis, C. et al. Modulation of Vascular Reactivity by Perivascular Adipose Tissue (PVAT). Curr Hypertens Rep 20, 44 (2018). https://doi.org/10.1007/s11906-018-0835-5

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