1932

Abstract

Excess visceral adipose tissue is associated with increased risk of high blood pressure, lipid disorders, type 2 diabetes, and cardiovascular disease. Adipose tissue is an endocrine organ with multiple humoral and metabolic roles in regulating whole-body physiology. However, perivascular adipose tissue (PVAT) also plays a functional role in regulating the contractile state of the underlying smooth muscle cell layer. Work during the past decade has shown that this adipose-vascular coupling is achieved by production of numerous substances released from PVAT. Animal disease models have been instrumental in identifying biological and pathophysiological functions of this regulation. These studies have produced strong evidence that alterations in the paracrine control of PVAT in the regulation of arterial tone contribute to vascular dysfunction in obesity, hypertension, and cardiometabolic disease. Perivascular relaxing factors, or perhaps their putative targets, might represent exciting new targets for the prevention and treatment of cardiovascular and metabolic diseases.

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2017-01-06
2024-06-15
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Literature Cited

  1. Stewart ST, Cutler DM, Rosen AB. 1.  2009. Forecasting the effects of obesity and smoking on U.S. life expectancy. N. Engl. J. Med. 361:2252–60 [Google Scholar]
  2. Lavie CJ, De Schutter A, Parto P, Jahangir E, Kokkinos P. 2.  et al. 2016. Obesity and prevalence of cardiovascular diseases and prognosis—the obesity paradox updated. Prog. Cardiovasc. Dis. 58:537–47 [Google Scholar]
  3. Hall JE, do Carmo JM, da Silva AA, Wang Z, Hall ME. 3.  2015. Obesity-induced hypertension: interaction of neurohumoral and renal mechanisms. Circ. Res. 116:991–1006 [Google Scholar]
  4. Chockalingam A, Campbell NR, Fodor JG. 4.  2006. Worldwide epidemic of hypertension. Can. J. Cardiol. 22:553–55 [Google Scholar]
  5. Vaneckova I, Maletinska L, Behuliak M, Nagelova V, Zicha J, Kunes J. 5.  2014. Obesity-related hypertension: possible pathophysiological mechanisms. J. Endocrinol. 223:R63–78 [Google Scholar]
  6. Fortuño A, Rodríguez A, Gómez-Ambrosi J, Frühbeck G, Díez J. 6.  2003. Adipose tissue as an endocrine organ: role of leptin and adiponectin in the pathogenesis of cardiovascular diseases. J. Physiol. Biochem. 59:51–60 [Google Scholar]
  7. Messerli FH, Sundgaard-Riise K, Reisin E, Dreslinski G, Dunn FG, Frohlich E. 7.  1983. Disparate cardiovascular effects of obesity and arterial hypertension. Am. J. Med. 74:808–12 [Google Scholar]
  8. Rocchini AP, Moorehead C, Katch V, Key J, Finta KM. 8.  1992. Forearm resistance vessel abnormalities and insulin resistance in obese adolescents. Hypertension 19:615–20 [Google Scholar]
  9. Zemel MB. 9.  1998. Nutritional and endocrine modulation of intracellular calcium: implications in obesity, insulin resistance and hypertension. Mol. Cell Biochem. 188:129–36 [Google Scholar]
  10. Boydens C, Maenhaut N, Pauwels B, Decaluwe K. de Voorde J. 10. , Van 2012. Adipose tissue as regulator of vascular tone. Curr. Hypertens. Rep. 14:270–78 [Google Scholar]
  11. Szasz T, Webb RC. 11.  2012. Perivascular adipose tissue: more than just structural support. Clin. Sci. 122:1–12 [Google Scholar]
  12. Maenhaut N, Van de Voorde J. 12.  2011. Regulation of vascular tone by adipocytes. BMC Med 9:25 [Google Scholar]
  13. Tano JY, Schleifenbaum J, Gollasch M. 13.  2014. Perivascular adipose tissue, potassium channels, and vascular dysfunction. Arterioscler. Thromb. Vasc. Biol. 34:1827–30 [Google Scholar]
  14. Yamawaki H, Tsubaki N, Mukohda M, Okada M, Hara Y. 14.  2010. Omentin, a novel adipokine, induces vasodilation in rat isolated blood vessels. Biochem. Biophys. Res. Commun. 393:668–72 [Google Scholar]
  15. Yamawaki H, Hara N, Okada M, Hara Y. 15.  2009. Visfatin causes endothelium-dependent relaxation in isolated blood vessels. Biochem. Biophys. Res. Commun. 383:503–8 [Google Scholar]
  16. Salcedo A, Garijo J, Monge L, Fernández N. García-Villalón A. 16. , Luis et al. 2007. Apelin effects in human splanchnic arteries. Role of nitric oxide and prostanoids. Regul. Pept. 144:50–55 [Google Scholar]
  17. Ohkawa F, Ikeda U, Kawasaki K, Kusano E, Igarashi M, Shimada K. 17.  1994. Inhibitory effect of interleukin-6 on vascular smooth muscle contraction. Am. J. Physiol. Heart Circ. Physiol. 266:H898–902 [Google Scholar]
  18. Loughrey JP, Laffey JG, Moore BJ, Lynch F, Boylan JF, McLoughlin P. 18.  2003. Interleukin-1β rapidly inhibits aortic endothelium-dependent relaxation by a DNA transcription-dependent mechanism. Crit. Care Med. 31:910–15 [Google Scholar]
  19. Gollasch M. 19.  2012. Vasodilator signals from perivascular adipose tissue. Br. J. Pharmacol. 165:633–42 [Google Scholar]
  20. Shek EW, Brands MW, Hall JE. 20.  1998. Chronic leptin infusion increases arterial pressure. Hypertension 31:409–14 [Google Scholar]
  21. Frühbeck G. 21.  1999. Pivotal role of nitric oxide in the control of blood pressure after leptin administration. Diabetes 48:903–8 [Google Scholar]
  22. Lembo G, Vecchione C, Fratta L, Marino G, Trimarco V. 22.  et al. 2000. Leptin induces direct vasodilation through distinct endothelial mechanisms. Diabetes 49:293–97 [Google Scholar]
  23. Carlyle M, Jones OB, Kuo JJ, Hall JE. 23.  2002. Chronic cardiovascular and renal actions of leptin: role of adrenergic activity. Hypertension 39:496–501 [Google Scholar]
  24. Momin AU, Melikian N, Shah AM, Grieve DJ, Wheatcroft SB. 24.  et al. 2006. Leptin is an endothelial-independent vasodilator in humans with coronary artery disease: evidence for tissue specificity of leptin resistance. Eur. Heart J. 27:2294–99 [Google Scholar]
  25. Kimura K, Tsuda K, Baba A, Kawabe T, Boh-oka S. 25.  et al. 2000. Involvement of nitric oxide in endothelium-dependent arterial relaxation by leptin. Biochem. Biophys. Res. Commun. 273:745–49 [Google Scholar]
  26. Sahin AS, Bariskaner H. 26.  2007. The mechanisms of vasorelaxant effect of leptin on isolated rabbit aorta. Fundam. Clin. Pharmacol. 21:595–600 [Google Scholar]
  27. Benkhoff S, Loot AE, Pierson I, Sturza A, Kohlstedt K. 27.  et al. 2012. Leptin potentiates endothelium-dependent relaxation by inducing endothelial expression of neuronal NO synthase. Arterioscler. Thromb. Vasc. Biol. 32:1605–12 [Google Scholar]
  28. do Carmo JM, da Silva AA, Wang Z, Freeman NJ, Alsheik AJ. 28.  et al. 2016. Regulation of blood pressure, appetite, and glucose by leptin after inactivation of insulin receptor substrate 2 signaling in the entire brain or in proopiomelanocortin neurons. Hypertension 67:378–86 [Google Scholar]
  29. do Carmo JM, da Silva AA, Cai Z, Lin S, Dubinion JH, Hall JE. 29.  2011. Control of blood pressure, appetite, and glucose by leptin in mice lacking leptin receptors in proopiomelanocortin neurons. Hypertension 57:918–26 [Google Scholar]
  30. Zhang H, Park Y, Zhang C. 30.  2010. Coronary and aortic endothelial function affected by feedback between adiponectin and tumor necrosis factor α in type 2 diabetic mice. Arterioscler. Thromb. Vasc. Biol. 30:2156–63 [Google Scholar]
  31. Wagner EM. 31.  2000. TNF-α induced bronchial vasoconstriction. Am. J. Physiol. Heart Circ. Physiol. 279:H946–51 [Google Scholar]
  32. Zhang DX, Yi FX, Zou AP, Li PL. 32.  2002. Role of ceramide in TNF-α-induced impairment of endothelium-dependent vasorelaxation in coronary arteries. Am. J. Physiol. Heart Circ. Physiol. 283:H1785–94 [Google Scholar]
  33. Baudry N, Vicaut E. 33.  1993. Role of nitric oxide in effects of tumor necrosis factor-alpha on microcirculation in rat. J. Appl. Physiol. 75:2392–99 [Google Scholar]
  34. Brian JE Jr., Faraci FM. 34.  1998. Tumor necrosis factor-α–induced dilatation of cerebral arterioles. Stroke 29:509–15 [Google Scholar]
  35. Johns DG, Webb RC. 35.  1998. TNF-α-induced endothelium-independent vasodilation: a role for phospholipase A2-dependent ceramide signaling. Am. J. Physiol. Heart Circ. Physiol. 275:H1592–98 [Google Scholar]
  36. Shibata M, Parfenova H, Zuckerman SL, Leffler CW. 36.  1996. Tumor necrosis factor-α induces pial arteriolar dilation in newborn pigs. Brain Res. Bull. 39:241–47 [Google Scholar]
  37. Cheranov SY, Jaggar JH. 37.  2006. TNF-α dilates cerebral arteries via NAD(P)H oxidase-dependent Ca2+ spark activation. Am. J. Physiol. Cell Physiol. 290:C964–71 [Google Scholar]
  38. Wimalasundera R, Fexby S, Regan L, Thom SAM, Hughes AD. 38.  2003. Effect of tumour necrosis factor-α and interleukin 1β on endothelium-dependent relaxation in rat mesenteric resistance arteries in vitro. Br. J. Pharmacol. 138:1285–94 [Google Scholar]
  39. Park Y, Yang J, Zhang H, Chen X, Zhang C. 39.  2011. Effect of PAR2 in regulating TNF-α and NAD(P)H oxidase in coronary arterioles in type 2 diabetic mice. Basic Res. Cardiol. 106:111–23 [Google Scholar]
  40. Yang J, Park Y, Zhang H, Xu X, Laine GA. 40.  et al. 2009. Feed-forward signaling of TNF-α and NF-κB via IKK-β pathway contributes to insulin resistance and coronary arteriolar dysfunction in type 2 diabetic mice. Am. J. Physiol. Heart Circ. Physiol. 296:H1850–58 [Google Scholar]
  41. Zhang C, Hein TW, Wang W, Ren Y, Shipley RD, Kuo L. 41.  2006. Activation of JNK and xanthine oxidase by TNF-α impairs nitric oxide-mediated dilation of coronary arterioles. J. Mol. Cell Cardiol. 40:247–57 [Google Scholar]
  42. Virdis A, Santini F, Colucci R, Duranti E, Salvetti G. 42.  et al. 2011. Vascular generation of tumor necrosis factor-α reduces nitric oxide availability in small arteries from visceral fat of obese patients. J. Am. Coll. Cardiol. 58:238–47 [Google Scholar]
  43. Virdis A, Duranti E, Rossi C, Dell'Agnello U, Santini E. 43.  et al. 2015. Tumour necrosis factor-alpha participates on the endothelin-1/nitric oxide imbalance in small arteries from obese patients: role of perivascular adipose tissue. Eur. Heart J. 36:784–94 [Google Scholar]
  44. Fésüs G, Dubrovska G, Gorzelniak K, Kluge R, Huang Y. 44.  et al. 2007. Adiponectin is a novel humoral vasodilator. Cardiovasc. Res. 75:719–27 [Google Scholar]
  45. Hong K, Lee S, Li R, Yang Y, Tanner MA. 45.  et al. 2016. Adiponectin receptor agonist, AdipoRon, causes vasorelaxation predominantly via a direct smooth muscle action. Microcirculation 23:207–20 [Google Scholar]
  46. Hattori Y, Suzuki M, Hattori S, Kasai K. 46.  2003. Globular adiponectin upregulates nitric oxide production in vascular endothelial cells. Diabetologia 46:1543–49 [Google Scholar]
  47. Chen H, Montagnani M, Funahashi T, Shimomura I, Quon MJ. 47.  2003. Adiponectin stimulates production of nitric oxide in vascular endothelial cells. J. Biol. Chem. 278:45021–26 [Google Scholar]
  48. Cheng KKY, Lam KSL, Wang Y, Huang Y, Carling D. 48.  et al. 2007. Adiponectin-induced endothelial nitric oxide synthase activation and nitric oxide production are mediated by APPL1 in endothelial cells. Diabetes 56:1387–94 [Google Scholar]
  49. Omae T, Nagaoka T, Tanano I, Yoshida A. 49.  2013. Adiponectin-induced dilation of isolated porcine retinal arterioles via production of nitric oxide from endothelial cells. Investig. Ophthalmol. Vis. Sci. 54:4586–94 [Google Scholar]
  50. Schmid PM, Resch M, Steege A, Fredersdorf-Hahn S, Stoelcker B. 50.  et al. 2011. Globular and full-length adiponectin induce NO-dependent vasodilation in resistance arteries of Zucker lean but not Zucker diabetic fatty rats. Am. J. Hypertens. 24:270–77 [Google Scholar]
  51. Dreier R, Asferg C, Berg JO, Andersen UB, Flyvbjerg A. 51.  et al. 2016. Similar adiponectin levels in obese normotensive and obese hypertensive men and no vasorelaxant effect of adiponectin on human arteries. Basic Clin. Pharmacol. Toxicol. 118:128–35 [Google Scholar]
  52. Ivkovic V, Jelakovic M, Laganovic M, Pecin I, Vrdoljak A. 52.  et al. 2014. Adiponectin is not associated with blood pressure in normotensives and untreated hypertensives with normal kidney function. Medicine 93:e250 [Google Scholar]
  53. Bassi M, do Carmo JM, Hall JE. Silva AA. 53. , da 2012. Chronic effects of centrally administered adiponectin on appetite, metabolism and blood pressure regulation in normotensive and hypertensive rats. Peptides 37:1–5 [Google Scholar]
  54. Sam F, Duhaney TA, Sato K, Wilson RM, Ohashi K. 54.  et al. 2010. Adiponectin deficiency, diastolic dysfunction, and diastolic heart failure. Endocrinology 151:322–31 [Google Scholar]
  55. Engeli S, Schling P, Gorzelniak K, Boschmann M, Janke J. 55.  et al. 2003. The adipose-tissue renin-angiotensin-aldosterone system: role in the metabolic syndrome?. Int. J. Biochem. Cell Biol. 35:807–25 [Google Scholar]
  56. Gálvez-Prieto B, Bolbrinker J, Stucchi P, de las Heras AI, Merino B. 56.  et al. 2008. Comparative expression analysis of the renin-angiotensin system components between white and brown perivascular adipose tissue. J. Endocrinol. 197:55–64 [Google Scholar]
  57. Riedel J, Badewien-Rentzsch B, Kohn B, Hoeke L, Einspanier R. 57.  2015. Characterization of key genes of the renin–angiotensin system in mature feline adipocytes and during in vitro adipogenesis. J. Anim. Physiol. Anim. Nutr. 1001139–48 [Google Scholar]
  58. Yiannikouris F, Karounos M, Charnigo R, English VL, Rateri DL. 58.  et al. 2012. Adipocyte-specific deficiency of angiotensinogen decreases plasma angiotensinogen concentration and systolic blood pressure in mice. Am. J. Physiol. Regul. Integr. Comp. Physiol. 302:R244–51 [Google Scholar]
  59. Yiannikouris F, Gupte M, Putnam K, Thatcher S, Charnigo R. 59.  et al. 2012. Adipocyte deficiency of angiotensinogen prevents obesity-induced hypertension in male mice. Hypertension 60:1524–30 [Google Scholar]
  60. Cinti S. 60.  2005. The adipose organ. Prostaglandins Leukot. Essent. Fat. Acids 73:9–15 [Google Scholar]
  61. Soltis EE, Cassis LA. 61.  1991. Influence of perivascular adipose tissue on rat aortic smooth muscle responsiveness. Clin. Exp. Hypertens. A 13:277–96 [Google Scholar]
  62. Löhn M, Dubrovska G, Lauterbach B, Luft FC, Gollasch M, Sharma AM. 62.  2002. Periadventitial fat releases a vascular relaxing factor. FASEB J. 16:1057–63 [Google Scholar]
  63. Dubrovska G, Verlohren S, Luft FC, Gollasch M. 63.  2004. Mechanisms of ADRF release from rat aortic adventitial adipose tissue. Am. J. Physiol. Heart Circ. Physiol. 286:H1107–13 [Google Scholar]
  64. Verlohren S, Dubrovska G, Tsang SY, Essin K, Luft FC. 64.  et al. 2004. Visceral periadventitial adipose tissue regulates arterial tone of mesenteric arteries. Hypertension 44:271–76 [Google Scholar]
  65. Gollasch M, Dubrovska G. 65.  2004. Paracrine role for periadventitial adipose tissue in the regulation of arterial tone. Trends Pharmacol. Sci. 25:647–53 [Google Scholar]
  66. Gao YJ, Zeng ZH, Teoh K, Sharma AM, Abouzahr L. 66.  et al. 2005. Perivascular adipose tissue modulates vascular function in the human internal thoracic artery. J. Thorac. Cardiovasc. Surg. 130:1130–36 [Google Scholar]
  67. Rittig K, Staib K, Machann J, Bottcher M, Peter A. 67.  et al. 2008. Perivascular fatty tissue at the brachial artery is linked to insulin resistance but not to local endothelial dysfunction. Diabetologia 51:2093–99 [Google Scholar]
  68. Reifenberger MS, Turk JR, Newcomer SC, Booth FW, Laughlin MH. 68.  2007. Perivascular fat alters reactivity of coronary artery: effects of diet and exercise. Med. Sci. Sports Exerc. 39:2125–34 [Google Scholar]
  69. Lu C, Zhao AX, Gao YJ, Lee RMKW. 69.  2011. Modulation of vein function by perivascular adipose tissue. Eur. J. Pharmacol. 657:111–16 [Google Scholar]
  70. Dashwood MR, Dooley A, Shi-Wen X, Abraham DJ, Souza DS. 70.  2007. Does periadventitial fat-derived nitric oxide play a role in improved saphenous vein graft patency in patients undergoing coronary artery bypass surgery?. J. Vasc. Res. 44:175–81 [Google Scholar]
  71. Verlohren S, Dubrovska G, Luft FC, Gollasch M. 71.  2004. Control of arterial tone by perivascular adipose tissue. Recent Res. Devel. Physiol. 2:259–64 [Google Scholar]
  72. Weston AH, Egner I, Dong Y, Porter EL, Heagerty AM, Edwards G. 72.  2013. Stimulated release of a hyperpolarizing factor (ADHF) from mesenteric artery perivascular adipose tissue: involvement of myocyte BKCa channels and adiponectin. Br. J. Pharmacol. 169:1500–9 [Google Scholar]
  73. Lynch FM, Withers SB, Yao Z, Werner ME, Edwards G. 73.  et al. 2013. Perivascular adipose tissue-derived adiponectin activates BKCa channels to induce anticontractile responses. Am. J. Physiol. Heart Circ. Physiol. 304:H786–95 [Google Scholar]
  74. Lee RMKW, Bader M, Alenina N, Santos RA, Gao YJ, Lu C. 74.  2011. Mas receptors in modulating relaxation induced by perivascular adipose tissue. Life Sci 89:467–72 [Google Scholar]
  75. Lee RMKW, Lu C, Su LY, Gao YJ. 75.  2009. Endothelium-dependent relaxation factor released by perivascular adipose tissue. J. Hypertens. 27:782–90 [Google Scholar]
  76. Gao YJ, Lu C, Su LY, Sharma AM, Lee RMKW. 76.  2007. Modulation of vascular function by perivascular adipose tissue: the role of endothelium and hydrogen peroxide. Br. J. Pharmacol. 151:323–31 [Google Scholar]
  77. Lee YC, Chang HH, Chiang CL, Liu CH, Yeh JI. 77.  et al. 2011. Role of perivascular adipose tissue–derived methyl palmitate in vascular tone regulation and pathogenesis of hypertension. Circulation 124:1160–71 [Google Scholar]
  78. Schleifenbaum J, Köhn C, Voblova N, Dubrovska G, Zavarirskaya O. 78.  et al. 2010. Systemic peripheral artery relaxation by KCNQ channel openers and hydrogen sulfide. J. Hypertens. 28:1875–82 [Google Scholar]
  79. Yang G, Wu L, Jiang B, Yang W, Qi J. 79.  et al. 2008. H2S as a physiologic vasorelaxant: hypertension in mice with deletion of cystathionine γ-lyase. Science 322:587–90 [Google Scholar]
  80. Feng X, Chen Y, Zhao J, Tang C, Jiang Z, Geng B. 80.  2009. Hydrogen sulfide from adipose tissue is a novel insulin resistance regulator. Biochem. Biophys. Res. Commun. 380:153–59 [Google Scholar]
  81. Gollasch M, Dubrovska G. 81.  2009. Adventitia-derived relaxing factor. J. Vasc. Res. 46:Suppl. 130 (Abstr. SSY–5) [Google Scholar]
  82. Fang L, Zhao J, Chen Y, Ma T, Xu G. 82.  et al. 2009. Hydrogen sulfide derived from periadventitial adipose tissue is a vasodilator. J. Hypertens. 27:2174–85 [Google Scholar]
  83. Emilova R, Dimitrova D, Mladenov M, Daneva T, Schubert R, Gagov H. 83.  2015. Cystathionine gamma-lyase of perivascular adipose tissue with reversed regulatory effect in diabetic rat artery. Biotechnol. Biotechnol. Equip. 29:147–51 [Google Scholar]
  84. Wojcicka G, Jamroz-Wisniewska A, Atanasova P, Chaldakov GN, Chylinska-Kula B, Beltowski J. 84.  2011. Differential effects of statins on endogenous H2S formation in perivascular adipose tissue. Pharmacol. Res. 63:68–76 [Google Scholar]
  85. Köhn C, Schleifenbaum J, Szijártó IA, Markó L, Dubrovska G. 85.  et al. 2012. Differential effects of cystathionine-γ-lyase–dependent vasodilatory H2S in periadventitial vasoregulation of rat and mouse aortas. PLOS ONE 7:e41951 [Google Scholar]
  86. Tangerman A. 86.  2009. Measurement and biological significance of the volatile sulfur compounds hydrogen sulfide, methanethiol and dimethyl sulfide in various biological matrices. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 877:3366–77 [Google Scholar]
  87. Tano JY, Gollasch M. 87.  2014. Hypoxia and ischemia-reperfusion: a BiK contribution?. Am. J. Physiol. Heart Circ. Physiol. 307:H811–17 [Google Scholar]
  88. Tano JY, Gollasch M. 88.  2014. Calcium-activated potassium channels in ischemia reperfusion: a brief update. Front. Physiol. 5:381 [Google Scholar]
  89. Withers SB, Passi N, Williams AS, de Freitas D, Heagerty AM. 89.  2013. Erythropoietin has a restorative effect on the contractility of arteries following experimental hypoxia. J. Cardiovasc. Dis. Res. 4:164–69 [Google Scholar]
  90. Zavaritskaya O, Zhuravleva N, Schleifenbaum J, Gloe T, Devermann L. 90.  et al. 2013. Role of KCNQ channels in skeletal muscle arteries and periadventitial vascular dysfunction. Hypertension 61:151–59 [Google Scholar]
  91. Schleifenbaum J, Kassmann M, Szijártκ IA, Hercule HC, Tano JY. 91.  et al. 2014. Stretch-activation of angiotensin II type 1a receptors contributes to the myogenic response of mouse mesenteric and renal arteries. Circ. Res. 115:263–72 [Google Scholar]
  92. Brueggemann LI, Moran CJ, Barakat JA, Yeh JZ, Cribbs LL, Byron KL. 92.  2007. Vasopressin stimulates action potential firing by protein kinase C-dependent inhibition of KCNQ5 in A7r5 rat aortic smooth muscle cells. Am. J. Physiol. Heart Circ. Physiol. 292:H1352–63 [Google Scholar]
  93. Yeung SY, Pucovský V, Moffatt JD, Saldanha L, Schwake M. 93.  et al. 2007. Molecular expression and pharmacological identification of a role for Kv7 channels in murine vascular reactivity. Br. J. Pharmacol. 151:758–70 [Google Scholar]
  94. Schwarz JR, Glassmeier G, Cooper EC, Kao TC, Nodera H. 94.  et al. 2006. KCNQ channels mediate IKs, a slow K+ current regulating excitability in the rat node of Ranvier. J. Physiol. 573:17–34 [Google Scholar]
  95. Koyama S, Appel SB. 95.  2006. Characterization of M-current in ventral tegmental area dopamine neurons. J. Neurophysiol. 96:535–43 [Google Scholar]
  96. Hadley JK, Passmore GM, Tatulian L, Al-Qatari M, Ye F. 96.  et al. 2003. Stoichiometry of expressed KCNQ2/KCNQ3 potassium channels and subunit composition of native ganglionic M channels deduced from block by tetraethylammonium. J. Neurosci. 23:5012–19 [Google Scholar]
  97. Shah MM, Mistry M, Marsh SJ, Brown DA, Delmas P. 97.  2002. Molecular correlates of the M-current in cultured rat hippocampal neurons. J. Physiol. 544:29–37 [Google Scholar]
  98. Hadley JK, Noda M, Selyanko AA, Wood IC, Abogadie FC, Brown DA. 98.  2000. Differential tetraethylammonium sensitivity of KCNQ1–4 potassium channels. Br. J. Pharmacol. 129:413–15 [Google Scholar]
  99. Suh BC, Hille B. 99.  2007. Electrostatic interaction of internal Mg2+ with membrane PIP2 seen with KCNQ K+ channels. J. Gen. Physiol. 130:241–56 [Google Scholar]
  100. Takemori K, Gao YJ, Ding L, Lu C, Su LY. 100.  et al. 2007. Elevated blood pressure in transgenic lipoatrophic mice and altered vascular function. Hypertension 49:365–72 [Google Scholar]
  101. Zeng ZH, Zhang ZH, Luo BH, He WK, Liang LY. 101.  et al. 2009. The functional changes of the perivascular adipose tissue in spontaneously hypertensive rats and the effects of atorvastatin therapy. Clin. Exp. Hypertens. 31:355–63 [Google Scholar]
  102. Plüger S, Faulhaber J, Fürstenau M, Löhn M, Waldschütz R. 102.  et al. 2000. Mice with disrupted BK channel β1 subunit gene feature abnormal Ca2+ spark/STOC coupling and elevated blood pressure. Circ. Res. 87:E53–60 [Google Scholar]
  103. Sausbier M, Arntz C, Bucurenciu I, Zhao H, Zhou XB. 103.  et al. 2005. Elevated blood pressure linked to primary hyperaldosteronism and impaired vasodilation in BK channel–deficient mice. Circulation 112:60–68 [Google Scholar]
  104. Huang F, Lezama MA, Ontiveros JA, Bravo G, Villafana S. 104.  et al. 2010. Effect of losartan on vascular function in fructose-fed rats: the role of perivascular adipose tissue. Clin. Exp. Hypertens. 32:98–104 [Google Scholar]
  105. Lu C, Su LY, Lee RM, Gao YJ. 105.  2010. Mechanisms for perivascular adipose tissue-mediated potentiation of vascular contraction to perivascular neuronal stimulation: the role of adipocyte-derived angiotensin II. Eur. J. Pharmacol. 634:107–12 [Google Scholar]
  106. Xia N, Horke S, Habermeier A, Closs EI, Reifenberg G. 106.  et al. 2016. Uncoupling of endothelial nitric oxide synthase in perivascular adipose tissue of diet-induced obese mice. Arterioscler. Thromb. Vasc. Biol. 36:78–85 [Google Scholar]
  107. Payne GA, Bohlen HG, Dincer UD, Borbouse L, Tune JD. 107.  2009. Periadventitial adipose tissue impairs coronary endothelial function via PKC-β-dependent phosphorylation of nitric oxide synthase. Am. J. Physiol. Heart Circ. Physiol. 297:H460–65 [Google Scholar]
  108. Mendizabal Y, Llorens S, Nava E. 108.  2013. Vasoactive effects of prostaglandins from the perivascular fat of mesenteric resistance arteries in WKY and SHROB rats. Life Sci 93:1023–32 [Google Scholar]
  109. Meyer MR, Fredette NC, Barton M, Prossnitz ER. 109.  2013. Regulation of vascular smooth muscle tone by adipose-derived contracting factor. PLOS ONE 8:e79245 [Google Scholar]
  110. Wang D, Wang C, Wu X, Zheng W, Sandberg K. 110.  et al. 2014. Endothelial dysfunction and enhanced contractility in microvessels from ovariectomized rats: roles of oxidative stress and perivascular adipose tissue. Hypertension 63:1063–69 [Google Scholar]
  111. Mann SE, Maille N, Clas D, Osol G. 111.  2015. Perivascular adipose tissue: a novel regulator of vascular tone in the rat pregnancy. Reprod. Sci. 22:802–7 [Google Scholar]
  112. Watts SW, Dorrance AM, Penfold ME, Rourke JL, Sinal CJ. 112.  et al. 2013. Chemerin connects fat to arterial contraction. Arterioscler. Thromb. Vasc. Biol. 33:1320–28 [Google Scholar]
  113. Ayala-Lopez N, Martini M, Jackson WF, Darios E, Burnett R. 113.  et al. 2014. Perivascular adipose tissue contains functional catecholamines. Pharmacol. Res. Perspect. 2:e00041 [Google Scholar]
  114. Ayala-Lopez N, Jackson WF, Burnett R, Wilson JN, Thompson JM, Watts SW. 114.  2015. Organic cation transporter 3 contributes to norepinephrine uptake into perivascular adipose tissue. Am. J. Physiol. Heart Circ. Physiol. 309:H1904–14 [Google Scholar]
  115. Lee MH, Chen SJ, Tsao CM, Wu CC. 115.  2014. Perivascular adipose tissue inhibits endothelial function of rat aortas via caveolin-1. PLOS ONE 9:e99947 [Google Scholar]
  116. Gao YJ, Takemori K, Su LY, An WS, Lu C. 116.  et al. 2006. Perivascular adipose tissue promotes vasoconstriction: the role of superoxide anion. Cardiovasc. Res. 71:363–73 [Google Scholar]
  117. Li R, Andersen I, Aleke J, Golubinskaya V, Gustafsson H, Nilsson H. 117.  2013. Reduced anti-contractile effect of perivascular adipose tissue on mesenteric small arteries from spontaneously hypertensive rats: role of Kv7 channels. Eur. J. Pharmacol. 698:310–15 [Google Scholar]
  118. Owen MK, Witzmann FA, McKenney ML, Lai X, Berwick ZC. 118.  et al. 2013. Perivascular adipose tissue potentiates contraction of coronary vascular smooth muscle: influence of obesity. Circulation 128:9–18 [Google Scholar]
  119. Gao YJ, Zeng ZH, Teoh K, Abouzahr L, Cybulsky I. 119.  et al. 2004. Perivascular adipose tissue releases a vasodilator in human internal thoracic artery. J. Vasc. Res. 41:20 [Google Scholar]
  120. Malinowski M, Deja MA, Janusiewicz P, Golba KS, Roleder T, Wos S. 120.  2013. Mechanisms of vasodilatatory effect of perivascular tissue of human internal thoracic artery. J. Physiol. Pharmacol. 64:309–16 [Google Scholar]
  121. Ozen G, Topal G, Gomez I, Ghorreshi A, Boukais K. 121.  et al. 2013. Control of human vascular tone by prostanoids derived from perivascular adipose tissue. Prostaglandins Other Lipid Med 107:13–17 [Google Scholar]
  122. Greenstein AS, Khavandi K, Withers SB, Sonoyama K, Clancy O. 122.  et al. 2009. Local inflammation and hypoxia abolish the protective anticontractile properties of perivascular fat in obese patients. Circulation 119:1661–70 [Google Scholar]
  123. Aghamohammadzadeh R, Unwin RD, Greenstein AS, Heagerty AM. 123.  2016. Effects of obesity on perivascular adipose tissue vasorelaxant function: nitric oxide, inflammation and elevated systemic blood pressure. J. Vasc. Res. 52:299–305 [Google Scholar]
  124. Aghamohammadzadeh R, Greenstein AS, Yadav R, Jeziorska M, Hama S. 124.  et al. 2013. Effects of bariatric surgery on human small artery function: evidence for reduction in perivascular adipocyte inflammation, and the restoration of normal anticontractile activity despite persistent obesity. J. Am. Coll. Cardiol. 62:128–35 [Google Scholar]
  125. Deja MA, Malinowski M, Golba KS, Piekarska M, Wos S. 125.  2015. Perivascular tissue mediated relaxation - a novel player in human vascular tone regulation. J. Physiol. Pharmacol. 66:841–46 [Google Scholar]
  126. Kociszewska K, Malinowski M, Czekaj P, Deja MA. 126.  2015. What is the source of anticontractile factor released by the pedicle of human internal thoracic artery?. Interact. Cardiovasc. Thorac. Surg. 21:301–7 [Google Scholar]
  127. Verhagen SN, Buijsrogge MP, Vink A, van Herwerden LA, van der Graaf Y, Visseren FL. 127.  2014. Secretion of adipocytokines by perivascular adipose tissue near stenotic and non-stenotic coronary artery segments in patients undergoing CABG. Atherosclerosis 233:242–47 [Google Scholar]
  128. Gil-Ortega M, Somoza B, Huang Y, Gollasch M, Fernández-Alfonso MS. 128.  2015. Regional differences in perivascular adipose tissue impacting vascular homeostasis. Trends Endocrinol. Metab. 26:367–75 [Google Scholar]
  129. Szijártó IA, Molnár GA, Mikolás E, Fisi V, Laczy B. 129.  et al. 2014. Increase in insulin-induced relaxation of consecutive arterial segments toward the periphery: role of vascular oxidative state. Free Rad. Res. 48:749–57 [Google Scholar]
  130. Szijártó IA, Molnár GA, Mikolás E, Fisi V, Cseh J. 130.  et al. 2014. Elevated vascular level of ortho-tyrosine contributes to the impairment of insulin-induced arterial relaxation. Horm. Metab. Res. 46:749–52 [Google Scholar]
  131. Meijer RI, Serne EH, Korkmaz HI, van der Peet DL, de Boer MP. 131.  et al. 2015. Insulin-induced changes in skeletal muscle microvascular perfusion are dependent upon perivascular adipose tissue in women. Diabetologia 58:1907–15 [Google Scholar]
  132. Zou L, Wang W, Liu S, Zhao X, Lyv Y. 132.  et al. 2016. Spontaneous hypertension occurs with adipose tissue dysfunction in perilipin-1 null mice. Biochim. Biophys. Acta 1862:182–91 [Google Scholar]
  133. Meijer RI, Bakker W, Alta CLAF, Sipkema P, Yudkin JS. 133.  et al. 2013. Perivascular adipose tissue control of insulin-induced vasoreactivity in muscle is impaired in db/db mice. Diabetes 62:590–98 [Google Scholar]
  134. de Boer MP, Meijer RI, Richter EA, van Nieuw Amerongen GP, Sipkema P. 134.  et al. 2016. Globular adiponectin controls insulin-mediated vasoreactivity in muscle through AMPKα2. Vascul. Pharmacol. 78:24–35 [Google Scholar]
  135. Eringa EC, Bakker W, van Hinsbergh VW. 135.  2012. Paracrine regulation of vascular tone, inflammation and insulin sensitivity by perivascular adipose tissue. Vascul. Pharmacol. 56:204–9 [Google Scholar]
  136. Hornstra JM, Serne EH, Eringa EC, Wijnker MC, de Boer MP. 136.  et al. 2013. Insulin's microvascular vasodilatory effects are inversely related to peripheral vascular resistance in overweight, but insulin-sensitive subjects. Obesity 21:2557–61 [Google Scholar]
  137. Rosei CA, De Ciuceis C, Rossini C, Porteri E, Rezzani R. 137.  et al. 2015. 7d.10: Effects of melatonin on contractile responses in small arteries of ageing mice. J. Hypertens. 33:Suppl. 1e103 [Google Scholar]
  138. Lee HY, Oh BH. 138.  2010. Aging and arterial stiffness. Circ. J. 74:2257–62 [Google Scholar]
  139. Fleenor BS, Eng JS, Sindler AL, Pham BT, Kloor JD, Seals DR. 139.  2014. Superoxide signaling in perivascular adipose tissue promotes age-related artery stiffness. Aging Cell 13:576–78 [Google Scholar]
  140. Du B, Ouyang A, Eng JS, Fleenor BS. 140.  2015. Aortic perivascular adipose-derived interleukin-6 contributes to arterial stiffness in low-density lipoprotein receptor deficient mice. Am. J. Physiol. Heart Circ. Physiol. 308:H1382–90 [Google Scholar]
  141. Bailey-Downs LC, Tucsek Z, Toth P, Sosnowska D, Gautam T. 141.  et al. 2013. Aging exacerbates obesity-induced oxidative stress and inflammation in perivascular adipose tissue in mice: a paracrine mechanism contributing to vascular redox dysregulation and inflammation. J. Gerontol. Ser. A Biol. Sci. Med. Sci. 68:780–92 [Google Scholar]
  142. Gao YJ, Holloway AC, Su LY, Takemori K, Lu C, Lee RMKW. 142.  2008. Effects of fetal and neonatal exposure to nicotine on blood pressure and perivascular adipose tissue function in adult life. Eur. J. Pharmacol. 590:264–68 [Google Scholar]
  143. Galvez B, de Castro J, Herold D, Dubrovska G, Arribas S. 143.  et al. 2006. Perivascular adipose tissue and mesenteric vascular function in spontaneously hypertensive rats. Arterioscler. Thromb. Vasc. Biol. 26:1297–302 [Google Scholar]
  144. Gálvez-Prieto B, Dubrovska G, Cano MV, Delgado M, Aranguez I. 144.  et al. 2008. A reduction in the amount and anti-contractile effect of periadventitial mesenteric adipose tissue precedes hypertension development in spontaneously hypertensive rats. Hypertens. Res. 31:1415–23 [Google Scholar]
  145. Marchesi C, Ebrahimian T, Angulo O, Paradis P, Schiffrin EL. 145.  2009. Endothelial nitric oxide synthase uncoupling and perivascular adipose oxidative stress and inflammation contribute to vascular dysfunction in a rodent model of metabolic syndrome. Hypertension 54:1384–92 [Google Scholar]
  146. Gil-Ortega M, Stucchi P, Guzmán-Ruiz R, Cano V, Arribas S. 146.  et al. 2010. Adaptative nitric oxide overproduction in perivascular adipose tissue during early diet-induced obesity. Endocrinology 151:3299–306 [Google Scholar]
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