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Alterations in Capillary and Microcirculatory Networks in Cardiovascular Diseases

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Microcirculation in Cardiovascular Diseases

Part of the book series: Updates in Hypertension and Cardiovascular Protection ((UHCP))

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Abstract

The capillary beds make up a dense network. Capillary diameter is typically the same or even smaller than the size of unstressed erythrocytes. In addition to its role in determining vascular resistance to flow (approximatively 15% of the total resistance), the capillary network is the region of the vascular system that specializes in the transport of substances between the blood and tissues. The distance of diffusion of O2 in tissues implies that the intercapillary distance cannot be greater than 100 μm in any living tissue.

Capillary density depends on the balance between the formation of neo-capillaries and the pruning of existing capillaries. Under stable physiological conditions, pro- and anti-angiogenic factors have equipotent effects on vessel density, thus ensuring a stable capillary density.

In clinical practice, capillary density is usually measured on the skin, on the forearm, or more frequently on the upper surface of a phalanx. Capillary rarefaction is a constant hallmark of both experimental and clinical hypertension. There is some evidence that capillary rarefaction in the skin may antedate the clinical onset of essential hypertension. The nitric oxide (NO) pathway and the renin–angiotensin system play a role in angiogenesis though likely in a complex fashion involving an interplay of antagonistic and context-dependent influences. Both systems are involved in the alterations of the microcirculation in both arterial hypertension and diabetes mellitus.

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References

  1. Smaje L, Zweifach BW, Intaglietta M. Micropressures and capillary filtration coefficients in single vessels of the cremaster muscle of the rat. Microvasc Res. 1970;2:96–110.

    Article  CAS  PubMed  Google Scholar 

  2. McCuskey RS, Reilly FD. Hepatic microvasculature: dynamic structure and its regulation. Semin Liver Dis. 1993;13:1–12.

    Article  CAS  PubMed  Google Scholar 

  3. Braverman IM. Ultrastructure and organization of the cutaneous microvasculature in normal and pathologic states. J Invest Dermatol. 1989;93:2S–9S.

    Article  CAS  PubMed  Google Scholar 

  4. Manelli A, Sangiorgi S, Ronga M, Reguzzoni M, Bini A, Raspanti M. Plexiform vascular structures in the human digital dermal layer: a SEM—corrosion casting morphological study. Eur J Morphol. 2005;42:173–7.

    Article  CAS  PubMed  Google Scholar 

  5. Froneck K, Zweifach BW. Microvascular pressure distribution in skeletal muscle and the effect of vasodilatation. Am J Phys. 1975;228:791–6.

    Article  Google Scholar 

  6. Dulling BR, Berne RM. Longitudinal gradients in periarteriolar oxygen tension: possible mechanism for the participation of oxygen in local regulation of blood flow. Circ Res. 1970;27:669–78.

    Article  Google Scholar 

  7. Helmlinger G, Yuan F, Dellian M, Jain RK. Interstitial pH and pO2 gradients in solid tumors in vivo: high-resolution measurements reveal a lack of correlation. Nat Med. 1997;3:177–82.

    Article  CAS  PubMed  Google Scholar 

  8. Flamme I, Frölich T, Risau. Molecular mechanisms of vasculogenesis and embryonic angiogenesis. J Cell Physiol. 1997;173:206–10.

    Article  CAS  PubMed  Google Scholar 

  9. Korn C, Augustin HG. Mechanisms of vessel pruning and regression. Dev Cell. 2015;34:5–17.

    Google Scholar 

  10. Noon JP, Walker BR, Webb DJ, Shore AC, Holton DW, Edwards HV, Watt GC. Impaired microvascular dilatation and capillary rarefaction in young adults with a predisposition to high blood pressure. J Clin Invest. 1997;99:1873–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Meirelles Pereira LM, Mandarim-de-Lacerda CA. Effect of antihypertensive drugs on the myocardial microvessels in rats with nitric oxide blockade. Pathol Res Pract. 2000;196:305–11.

    Article  CAS  PubMed  Google Scholar 

  12. Struijker Boudier HA, le Noble JL, Messing MW, Huijberts MS, le Noble FA, van Essen H. The microcirculation and hypertension. J Hypertens. 1992;10(suppl):S147–56.

    CAS  Google Scholar 

  13. Levy BI, Ambrosio G, Pries AR, Struijker-Boudier HAJ. Microcirculation in hypertension–a new target for treatment? Circulation. 2001;104:735–40.

    Article  CAS  PubMed  Google Scholar 

  14. Feihl F, Liaudet L, Waeber B, Levy BI. Hypertension: a disease of the microcirculation? Hypertension. 2006;48:1012–7.

    Article  CAS  PubMed  Google Scholar 

  15. Prewitt RL, Chen II, Dowell R. Development of microvascular rarefaction in the spontaneously hypertensive rat. Am J Phys. 1982;243:H243–51.

    CAS  Google Scholar 

  16. Chen II, Prewitt RL, Dowell RF. Microvascular rarefaction in spontaneously hypertensive rat cremaster muscle. Am J Phys. 1981;241:H306–10.

    CAS  Google Scholar 

  17. Boegehold MA, Johnson MD, Overbeck HW. Pressure-independent arteriolar rarefaction in hypertension. Am J Phys. 1991;261:H83–7.

    CAS  Google Scholar 

  18. Henrich H, Hertel R, Assmann R. Structural differences in the mesentery microcirculation between normotensive and spontaneously hypertensive rats. Pflugers Arch. 1978;375:153–9.

    Article  CAS  PubMed  Google Scholar 

  19. Haack DW, Schaffer JJ, Simpson JG. Comparisons of cutaneous microvessels from spontaneously hypertensive, normotensive Wistar-Kyoto, and normal Wistar rats. Proc Soc Exp Biol Med. 1980;164:453–8.

    Article  CAS  PubMed  Google Scholar 

  20. Lin SZ, Sposito N, Pettersen S, Rybacki L, McKenna E, Pettigrew K, Fenstermacher J. Cerebral capillary bed structure of normotensive and chronically hypertensive rats. Microvasc Res. 1990;40:341–57.

    Article  CAS  PubMed  Google Scholar 

  21. Rakusan K, Cicutti N, Kazda S, Turek Z. Effect of nifedipine on coronary capillary geometry in normotensive and hypertensive rats. Hypertension. 1994;24:205–11.

    Article  CAS  PubMed  Google Scholar 

  22. Sabri A, Samuel JL, Marotte F, Poitevin P, Rappaport L, Levy BI. Microvasculature in angiotensin II-dependent cardiac hypertrophy in the rat. Hypertension. 1998;32:371–5.

    Article  CAS  PubMed  Google Scholar 

  23. Kobayashi N, Kobayashi K, Hara K, Higashi T, Yanaka H, Yagi S, Matsuoka H. Benidipine stimulates nitric oxide synthase and improves coronary circulation in hypertensive rats. Am J Hypertens. 1999;12:483–91.

    Article  CAS  PubMed  Google Scholar 

  24. Rakusan K, Cicutti N, Maurin A, Guez D, Schiavi P. The effect of treatment with low dose ACE inhibitor and/or diuretic on coronary microvasculature in stroke-prone spontaneously hypertensive rats. Microvasc Res. 2000;59:243–54.

    Article  CAS  PubMed  Google Scholar 

  25. Levy BI, Duriez M, Samuel JL. Coronary microvasculature alteration in hypertensive rats. Effect of treatment with a diuretic and an ACE inhibitor. Am J Hypertens. 2001;14:7–13.

    Article  CAS  PubMed  Google Scholar 

  26. Tomanek RJ, Searls JC, Lachenbruch PA. Quantitative changes in the capillary bed during developing, peak, and stabilized cardiac hypertrophy in the spontaneously hypertensive rat. Circ Res. 1982;51:295–304.

    Article  CAS  PubMed  Google Scholar 

  27. Rakusan K, Flanagan MF, Geva T, Southern J, Van Praagh R. Morphometry of human coronary capillaries during normal growth and the effect of age in left ventricular pressure-overload hypertrophy. Circulation. 1992;86:38–46.

    Article  CAS  PubMed  Google Scholar 

  28. Ruedemann AD. Conjunctival vessels. J Am Med Assoc. 1933;101:1477–81.

    Article  Google Scholar 

  29. Sullivan JM, Prewitt RL, Josephs JA. Attenuation of the microcirculation in young patients with high-output borderline hypertension. Hypertension. 1983;5:844–51.

    Article  CAS  PubMed  Google Scholar 

  30. Serne EH, Gans ROB, ter Maaten JC, Tangelder GJ, Donker AJM, Stehouwer CDA. Impaired skin capillary recruitment in essential hypertension is caused by both functional and structural capillary rarefaction. Hypertension. 2001;38:238–42.

    Article  CAS  PubMed  Google Scholar 

  31. Antonios TFT, Singer DRJ, Markandu ND, Mortimer PS, MacGregor GA. Structural skin capillary rarefaction in essential hypertension. Hypertension. 1999;33:998–1001.

    Article  CAS  PubMed  Google Scholar 

  32. Prasad A, Dunnill GS, Mortimer PS, MacGregor GA. Capillary rarefaction in the forearm skin in essential hypertension. J Hypertens. 1995;13:265–8.

    CAS  PubMed  Google Scholar 

  33. Antonios TFT, Singer DRJ, Markandu ND, Mortimer PS, MacGregor GA. Rarefaction of skin capillaries in borderline essential hypertension suggests an early structural abnormality. Hypertension. 1999;34:655–8.

    Article  CAS  PubMed  Google Scholar 

  34. Antonios TFT, Rattray FM, Singer DRJ, Markandu ND, Mortimer PS, MacGregor GA. Rarefaction of skin capillaries in normotensive offspring of individuals with essential hypertension. Heart. 2003;89:175–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Debbabi H, Uzan L, Mourad JJ, Safar M, Levy BI, Tibirica E. Increased skin capillary density in treated essential hypertensive patients. Am J Hypertens. 2006;19:477–83.

    Article  PubMed  Google Scholar 

  36. Kubis N, Besnard S, Silvestre JS, Feletou M, Huang PL, Levy BI, Tedgui A. Decreased arteriolar density in endothelial nitric oxide synthase knockout mice is due to hypertension, not to the constitutive defect in endothelial nitric oxide synthase enzyme. J Hypertens. 2002;20:273–80.

    Article  CAS  PubMed  Google Scholar 

  37. Kobayashi N, DeLano FA, Schmid-Schönbein GW. Oxidative stress promotes endothelial cell apoptosis and loss of microvessels in the spontaneously hypertensive rats. Arterioscler Thromb Vasc Biol. 2005;25:2114–21.

    Article  CAS  PubMed  Google Scholar 

  38. Lee PC, Salyapongse AN, Bragdon GA, Shears LL 2nd, Watkins SC, Edington HD, Billiar TR. Impaired wound healing and angiogenesis in eNOS-deficient mice. Am J Phys. 1999;277:H1600–8.

    CAS  Google Scholar 

  39. Dulak J, Jozkowicz A, Dembinska-Kiec A, Guevara I, Zdzienicka A, Zmudzinska-Grochot D, Florek I, Wojtowicz A, Szuba A, Cooke JP. Nitric oxide induces the synthesis of vascular endothelial growth factor by rat vascular smooth muscle cells. Arterioscler Thromb Vasc Biol. 2000;20:659–66.

    Article  CAS  PubMed  Google Scholar 

  40. Kiefer FN, Misteli H, Kalak N, Tschudin K, Fingerle J, Van der Kooij M, Stumm M, Sumanovski LT, Sieber CC, Battegay EJ. Inhibition of NO biosynthesis, but not elevated blood pressure, reduces angiogenesis in rat models of secondary hypertension. Blood Press. 2002;11:116–24.

    Article  CAS  PubMed  Google Scholar 

  41. Sasaki K, Murohara T, Ikeda H, Sugaya T, Shimada T, Shintani S, Imaizumi T. Evidence for the importance of angiotensin II type 1 receptor in ischemia-induced angiogenesis. J Clin Invest. 2002;109:603–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Munzenmaier DH, Greene AS. Opposing actions of angiotensin II on microvascular growth and arterial blood pressure. Hypertension. 1996;27:760–5.

    Article  CAS  PubMed  Google Scholar 

  43. Emanueli C, Salis MB, Stacca T, Pinna A, Gaspa L, Madeddu P. Angiotensin AT(1) receptor signalling modulates reparative angiogenesis induced by limb ischaemia. Br J Pharmacol. 2002;135:87–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Walther T, Menrad A, Orzechowski HD, Siemeister G, Paul M, Schirner M. Differential regulation of in vivo angiogenesis by angiotensin II receptors. FASEB J. 2003;17:2061–7.

    Article  CAS  PubMed  Google Scholar 

  45. de Boer RA, Pinto YM, Suurmeijer AJ, Pokharel S, Scholtens E, Humler M, Saavedra JM, Boomsma F, van Gilst WH, van Veldhuisen DJ. Increased expression of cardiac angiotensin II type 1 (AT(1)) receptors decreases myocardial microvessel density after experimental myocardial infarction. Cardiovasc Res. 2003;57:434–42.

    Article  PubMed  Google Scholar 

  46. Forder JP, Munzenmaier DH, Greene AS. Angiogenic protection from focal ischemia with angiotensin II type 1 receptor blockade in the rat. Am J Phys. 2005;288:H1989–96.

    CAS  Google Scholar 

  47. Silvestre JS, Tamarat R, Senbonmatsu T, Icchiki T, Ebrahimian T, Iglarz M, Besnard S, Duriez M, Inagami T, Levy BI. Antiangiogenic effect of angiotensin II type 2 receptor in ischemia-induced angiogenesis in mice hindlimb. Circ Res. 2002;90:1072–9.

    Article  CAS  PubMed  Google Scholar 

  48. Benndorf R, Boger RH, Ergun S, Steenpass A, Wieland T. Angiotensin II type 2 receptor inhibits vascular endothelial growth factor-induced migration and in vitro tube formation of human endothelial cells. Circ Res. 2003;93:438–47.

    Article  CAS  PubMed  Google Scholar 

  49. AbdAlla S, Lother H, Abdel-tawab AM, Quitterer U. The angiotensin II AT2 receptor is an AT1 receptor antagonist. J Biol Chem. 2001;276:39721–6.

    Article  CAS  PubMed  Google Scholar 

  50. Tsutsumi Y, Matsubara H, Masaki H, Kurihara H, Murasawa S, Takai S, Miyazaki M, Nozawa Y, Ozono R, Nakagawa K, Miwa T, Kawada N, Mori Y, Shibasaki Y, Tanaka Y, Fujiyama S, Koyama Y, Fujiyama A, Takahashi H, Iwasaka T. Angiotensin II type 2 receptor overexpression activates the vascular kinin system and causes vasodilation. J Clin Invest. 1999;104:925–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Silvestre JS, Bergaya S, Tamarat R, Duriez M, Boulanger CM, Levy BI. Proangiogenic effect of angiotensin-converting enzyme inhibition is mediated by the bradykinin B(2) receptor pathway. Circ Res. 2001;89:678–83.

    Article  CAS  PubMed  Google Scholar 

  52. Silvestre JS, Smadja DM, Lévy BI. Postischemic revascularization: from cellular and molecular mechanisms to clinical applications. Physiol Rev. 2013;93:1743–802.

    Article  CAS  PubMed  Google Scholar 

  53. Tesfamariam B, Brown ML, Deykin D, Cohen RA. Elevated glucose promotes generation of endothelium-derived vasoconstrictor prostanoids in rabbit aorta. J Clin Invest. 1990;85:929–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Pieper GM, Peltier BA. Amelioration by L-arginine of a dysfunctional arginine/nitric oxide pathway in diabetic endothelium. J Cardiovasc Pharmacol. 1995;25:397–403.

    Article  CAS  PubMed  Google Scholar 

  55. Abaci A, Oguzhan A, Kahraman S, Eryol NK, Unal S, Arinc H, et al. Effect of diabetes mellitus on formation of coronary collateral vessels. Circulation. 1999;99:2239–42.

    Article  CAS  PubMed  Google Scholar 

  56. Parenti A, Morbidelli L, Cui XL, Douglas JG, Hood JD, Granger HJ, et al. Nitric oxide is an upstream signal of vascular endothelial growth factor-induced extracellular signal-regulated kinase1/2 activation in postcapillary endothelium. J Biol Chem. 1998;273(7):4220–6.

    Article  CAS  PubMed  Google Scholar 

  57. Goligorsky MS. Microvascular rarefaction: the decline and fall of blood vessels. Organogenesis. 2010;6:1–10.

    Article  PubMed  PubMed Central  Google Scholar 

  58. Kivela R, Silvennoinen M, Touvra AM, Lehti TM, Kainulainen H, Vihko V. Effects of experimental type 1 diabetes and exercise training on angiogenic gene expression and capillarization in skeletal muscle. FASEB J. 2006;20:1570–2.

    Article  CAS  PubMed  Google Scholar 

  59. Ebrahimian TG, Heymes C, You D, Blanc-Brude O, Mees B, Waeckel L, Duriez M, Vilar J, Brandes RP, Levy BI, Shah AM, Silvestre JS. NADPH oxidase-derived overproduction of reactive oxygen species impairs postischemic neovascularization in mice with type 1 diabetes. Am J Pathol. 2006;169:719–1728.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Kida Y, Tchao BN, Yamaguchi I. Peritubular capillary rarefaction: a new therapeutic target in chronic kidney disease. Pediatr Nephrol. 2014;29:333–42.

    Article  PubMed  Google Scholar 

  61. Howangyin KY, Silvestre JS. Diabetes mellitus and ischemic diseases: molecular mechanisms of vascular repair dysfunction. Arterioscler Thromb Vasc Biol. 2014;34:1126–35.

    Article  CAS  PubMed  Google Scholar 

  62. Jaap AJ, Shore AC, Stockman AJ, Tooke JE. Skin capillary density in subjects with impaired glucose tolerance and patients with type 2 diabetes. Diabet Med. 1996;13:160–1604.

    Article  CAS  PubMed  Google Scholar 

  63. Fenton BM, Zweifach BW, Worthen DM. Quantitative morphometry of conjunctival microcirculation in diabetes mellitus. Microvasc Res. 1979;18:153–1566.

    Article  CAS  PubMed  Google Scholar 

  64. Clark MG, Barrett EJ, Wallis MG, Vincent MA, Rattigan S. The microvasculature in insulin resistance and type 2 diabetes. Semin Vasc Med. 2002;2:21–31.

    Article  PubMed  Google Scholar 

  65. Aellen J, Dabiri A, Heim A, Liaudet L, Burnier M, Ruiz J, et al. Preserved capillary density of dorsal finger skin in treated hypertensive patients with or without type 2 diabetes. Microcirculation. 2012;19:554–62.

    Article  PubMed  Google Scholar 

  66. Rizzoni D, Porteri E, Duse S, De Ciuceis C, Agabiti-Rosei C, La Boria E, et al. Relationship between media-to-lumen ratio of subcutaneous small arteries and wall-to-lumen ratio of retinal arterioles evaluated noninvasively by scanning laser Doppler flowmetry. J Hypertens. 2012;30:1169–75.

    Google Scholar 

  67. Kaiser SE, Sanjuliani AF, Estato V, Gomes MB, Tibirica E. Antihypertensive treatment improves microvascular rarefaction and reactivity in low-risk hypertensive individuals. Microcirculation. 2013;20:703–16.

    Google Scholar 

  68. Tomassoni D, Mancinelli G, Mignini F, Sabbatini M, Amenta F. Quantitative image analysis of choroid and retinal vasculature in SHR: a model of cerebrovascular hypertensive changes? Clin Exp Hypertens. 2002;24:741–52.

    Article  PubMed  Google Scholar 

  69. Muiesan ML, Salvetti M, Rizzoni D, Paini A, Agabiti-Rosei C, Aggiusti C, et al. Resistant hypertension and target organ damage. Hypertens Res. 2013;36:485–91.

    Article  PubMed  Google Scholar 

  70. Lorenzi M, Gerhardinger C. Early cellular and molecular changes induced by diabetes in the retina. Diabetologia. 2001;44:791–804.

    Article  CAS  PubMed  Google Scholar 

  71. Jumar A, Harazny JM, Ott C, Friedrich S, Kistner I, Striepe K, Schmieder RE. Retinal capillary rarefaction in patients with type 2 diabetes mellitus. PLoS One. 2016;11:e0162608.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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  1. Inserm U970, PARCC & Vessels and Blood Institute, Paris, France

    Bernard I. Levy

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  1. Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy

    Enrico Agabiti-Rosei

  2. Division of Cardiovascular Sciences School of Medical Sciences, University of Manchester, Manchester, UK

    Anthony M. Heagerty

  3. Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy

    Damiano Rizzoni

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Levy, B.I. (2020). Alterations in Capillary and Microcirculatory Networks in Cardiovascular Diseases. In: Agabiti-Rosei, E., Heagerty, A.M., Rizzoni, D. (eds) Microcirculation in Cardiovascular Diseases. Updates in Hypertension and Cardiovascular Protection. Springer, Cham. https://doi.org/10.1007/978-3-030-47801-8_10

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