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Pathophysiology of Hypertension

  • Chapter
Pathophysiology and Pharmacotherapy of Cardiovascular Disease

Abstract

Hypertension is a rather simple phenotype characterized by an increase in systemic blood pressure above an arbitrarily defined threshold. Yet, the mechanisms leading to the increase in blood pressure are extremely complex and involved a wide variety of neurohormonal, renal, metabolic, and vascular factors. The causes of hypertension differ substantially in young children, in middle-aged men and women, and in the elderly. In children, hypertension is often the appearance of a renal or endocrine disease, whereas in adults, the large majority of patients with hypertension have an essential hypertension, a denomination reflecting that the mechanisms are not fully understood although some well-defined pathogenic factors have been described in patients with hypertension associated with diabetes mellitus, obesity, hyperaldosteronism, renovascular hypertension, or renal diseases. In the elderly, hypertension is strongly associated with factors leading to vascular aging and loss of arterial elasticity. The purpose of this chapter is to review the pathophysiology of hypertension in these different clinical situations in light of the recent literature.

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References

  1. Lozano R, et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012;380(9859):2095–128.

    Article  PubMed  Google Scholar 

  2. Hajjar I, Kotchen TA. Trends in prevalence, awareness, treatment, and control of hypertension in the United States, 1988–2000. JAMA. 2003;290(2):199–206.

    Article  PubMed  Google Scholar 

  3. Ostchega Y, et al. Trends of elevated blood pressure among children and adolescents: data from the National Health and Nutrition Examination Survey 1988–2006. Am J Hypertens. 2009;22(1):59–67.

    Article  PubMed  Google Scholar 

  4. Barker DJ, et al. Growth in utero, blood pressure in childhood and adult life, and mortality from cardiovascular disease. BMJ. 1989;298(6673):564–7.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  5. Moritz KM, et al. Developmental programming of a reduced nephron endowment: more than just a baby’s birth weight. Am J Physiol Renal Physiol. 2009;296(1):F1–9.

    Article  CAS  PubMed  Google Scholar 

  6. Lurbe E, et al. Management of high blood pressure in children and adolescents: recommendations of the European Society of Hypertension. J Hypertens. 2009;27(9):1719–42.

    Article  CAS  PubMed  Google Scholar 

  7. Chiolero A, et al. Prevalence of hypertension in schoolchildren based on repeated measurements and association with overweight. J Hypertens. 2007;25(11):2209–17.

    Article  CAS  PubMed  Google Scholar 

  8. Chiolero A, et al. Discordant secular trends in elevated blood pressure and obesity in children and adolescents in a rapidly developing country. Circulation. 2009;119(4):558–65.

    Article  PubMed  Google Scholar 

  9. Portman RJ, et al. Pediatric hypertension: diagnosis, evaluation, management, and treatment for the primary care physician. Curr Probl Pediatr Adolesc Health Care. 2005;35(7):262–94.

    Article  PubMed  Google Scholar 

  10. Brown NJ. Contribution of aldosterone to cardiovascular and renal inflammation and fibrosis. Nat Rev Nephrol. 2013;9(8):459–69.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  11. Bondanelli M, Ambrosio MR, degli Uberti EC. Pathogenesis and prevalence of hypertension in acromegaly. Pituitary. 2001;4(4):239–49.

    Article  CAS  PubMed  Google Scholar 

  12. Kamenicky P, et al. Body fluid expansion in acromegaly is related to enhanced epithelial sodium channel (ENaC) activity. J Clin Endocrinol Metab. 2011;96(7):2127–35.

    Article  CAS  PubMed  Google Scholar 

  13. Rosskopf D, et al. Genetics of arterial hypertension and hypotension. Naunyn Schmiedebergs Arch Pharmacol. 2007;374(5–6):429–69.

    Article  CAS  PubMed  Google Scholar 

  14. Stabouli S, Kotsis V, Zakopoulos N. Ambulatory blood pressure monitoring and target organ damage in pediatrics. J Hypertens. 2007;25(10):1979–86.

    Article  CAS  PubMed  Google Scholar 

  15. Guyton AC. Long-term arterial pressure control: an analysis from animal experiments and computer and graphic models. Am J Physiol. 1990;259(5 Pt 2):R865–77.

    CAS  PubMed  Google Scholar 

  16. Ivy JR, Bailey MA. Pressure natriuresis and the renal control of arterial blood pressure. J Physiol. 2014;592(Pt 18):3955–67.

    Article  CAS  PubMed  Google Scholar 

  17. Rettig R, Grisk O. The kidney as a determinant of genetic hypertension: evidence from renal transplantation studies. Hypertension. 2005;46(3):463–8.

    Article  CAS  PubMed  Google Scholar 

  18. Crowley SD, et al. Distinct roles for the kidney and systemic tissues in blood pressure regulation by the renin-angiotensin system. J Clin Invest. 2005;115(4):1092–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  19. Curtis JJ, et al. Remission of essential hypertension after renal transplantation. N Engl J Med. 1983;309(17):1009–15.

    Article  CAS  PubMed  Google Scholar 

  20. Lifton RP, Gharavi AG, Geller DS. Molecular mechanisms of human hypertension. Cell. 2001;104(4):545–56.

    Article  CAS  PubMed  Google Scholar 

  21. Fava C, et al. 24-h ambulatory blood pressure is linked to chromosome 18q21-22 and genetic variation of NEDD4L associates with cross-sectional and longitudinal blood pressure in Swedes. Kidney Int. 2006;70(3):562–9.

    CAS  PubMed  Google Scholar 

  22. Fava C, et al. Subjects heterozygous for genetic loss of function of the thiazide-sensitive cotransporter have reduced blood pressure. Hum Mol Genet. 2008;17(3):413–8.

    Article  CAS  PubMed  Google Scholar 

  23. Kobori H, et al. The intrarenal renin-angiotensin system: from physiology to the pathobiology of hypertension and kidney disease. Pharmacol Rev. 2007;59(3):251–87.

    Article  CAS  PubMed  Google Scholar 

  24. Lombardi D, et al. Salt-sensitive hypertension develops after short-term exposure to Angiotensin II. Hypertension. 1999;33(4):1013–9.

    Article  CAS  PubMed  Google Scholar 

  25. Franco M, et al. Impaired pressure natriuresis resulting in salt-sensitive hypertension is caused by tubulointerstitial immune cell infiltration in the kidney. Am J Physiol Renal Physiol. 2013;304(7):F982–90.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  26. DiBona GF, Kopp UC. Neural control of renal function. Physiol Rev. 1997;77(1):75–197.

    CAS  PubMed  Google Scholar 

  27. DiBona GF, Esler M. Translational medicine: the antihypertensive effect of renal denervation. Am J Physiol Regul Integr Comp Physiol. 2010;298(2):R245–53.

    Article  CAS  PubMed  Google Scholar 

  28. Julius S. Autonomic nervous system dysregulation in human hypertension. Am J Cardiol. 1991;67(10):3B–7.

    Article  CAS  PubMed  Google Scholar 

  29. Krum H, et al. Novel procedure- and device-based strategies in the management of systemic hypertension. Eur Heart J. 2011;32(5):537–44.

    Article  PubMed  Google Scholar 

  30. Patrono C. The PGH-synthase system and isozyme-selective inhibition. J Cardiovasc Pharmacol. 2006;47 Suppl 1:S1–6.

    Article  CAS  PubMed  Google Scholar 

  31. Harris Jr RC. Cyclooxygenase-2 inhibition and renal physiology. Am J Cardiol. 2002;89(6A):10D–7.

    Article  CAS  PubMed  Google Scholar 

  32. Harris RC, et al. Cyclooxygenase-2 is associated with the macula densa of rat kidney and increases with salt restriction. J Clin Invest. 1994;94(6):2504–10.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  33. Lin L, et al. Role of prostanoids in renin-dependent and renin-independent hypertension. Hypertension. 1991;17(4):517–25.

    Article  CAS  PubMed  Google Scholar 

  34. Fujino T, et al. Decreased susceptibility to renovascular hypertension in mice lacking the prostaglandin I2 receptor IP. J Clin Invest. 2004;114(6):805–12.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  35. Cinotti GA, Pugliese F. Prostaglandins and hypertension. Am J Hypertens. 1989;2(2 Pt 2):10S–5.

    Article  CAS  PubMed  Google Scholar 

  36. Hornych A, et al. Thromboxane B2 in borderline and essential hypertensive patients. Prostaglandins Leukot Med. 1983;10(2):145–55.

    Article  CAS  PubMed  Google Scholar 

  37. Sowers JR, et al. The Effects of cyclooxygenase-2 inhibitors and nonsteroidal anti-inflammatory therapy on 24-hour blood pressure in patients with hypertension, osteoarthritis, and type 2 diabetes mellitus. Arch Intern Med. 2005;165(2):161–8.

    Article  CAS  PubMed  Google Scholar 

  38. Folkow B. Acute effects of pressure on resistance vessel geometry. Acta Physiol Scand. 1978;104(4):496–8.

    Article  CAS  PubMed  Google Scholar 

  39. Takeshita A, Mark AL. Decreased vasodilator capacity of forearm resistance vessels in borderline hypertension. Hypertension. 1980;2(5):610–6.

    Article  CAS  PubMed  Google Scholar 

  40. Mulvany MJ. Small artery remodelling in hypertension. Basic Clin Pharmacol Toxicol. 2012;110(1):49–55.

    Article  CAS  PubMed  Google Scholar 

  41. Bakker EN, et al. Organoid culture of cannulated rat resistance arteries: effect of serum factors on vasoactivity and remodeling. Am J Physiol Heart Circ Physiol. 2000;278(4):H1233–40.

    CAS  PubMed  Google Scholar 

  42. Bakker EN, et al. Small artery remodeling depends on tissue-type transglutaminase. Circ Res. 2005;96(1):119–26.

    Article  CAS  PubMed  Google Scholar 

  43. Vane JR, Anggard EE, Botting RM. Regulatory functions of the vascular endothelium. N Engl J Med. 1990;323(1):27–36.

    Article  CAS  PubMed  Google Scholar 

  44. Furchgott RF, Zawadzki JV. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature. 1980;288(5789):373–6.

    Article  CAS  PubMed  Google Scholar 

  45. Konishi M, Su C. Role of endothelium in dilator responses of spontaneously hypertensive rat arteries. Hypertension. 1983;5(6):881–6.

    Article  CAS  PubMed  Google Scholar 

  46. Luscher TF, Raij L, Vanhoutte PM. Endothelium-dependent vascular responses in normotensive and hypertensive Dahl rats. Hypertension. 1987;9(2):157–63.

    Article  CAS  PubMed  Google Scholar 

  47. Panza JA, et al. Abnormal endothelium-dependent vascular relaxation in patients with essential hypertension. N Engl J Med. 1990;323(1):22–7.

    Article  CAS  PubMed  Google Scholar 

  48. Miller MJ, Pinto A, Mullane KM. Impaired endothelium-dependent relaxations in rabbits subjected to aortic coarctation hypertension. Hypertension. 1987;10(2):164–70.

    Article  CAS  PubMed  Google Scholar 

  49. Taddei S, et al. Aging and endothelial function in normotensive subjects and patients with essential hypertension. Circulation. 1995;91(7):1981–7.

    Article  CAS  PubMed  Google Scholar 

  50. Huang PL, et al. Hypertension in mice lacking the gene for endothelial nitric oxide synthase. Nature. 1995;377(6546):239–42.

    Article  CAS  PubMed  Google Scholar 

  51. Van Vliet BN, Chafe LL, Montani JP. Characteristics of 24 h telemetered blood pressure in eNOS-knockout and C57Bl/6J control mice. J Physiol. 2003;549(Pt 1):313–25.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  52. Schiffrin EL. A critical review of the role of endothelial factors in the pathogenesis of hypertension. J Cardiovasc Pharmacol. 2001;38 Suppl 2:S3–6.

    Article  CAS  PubMed  Google Scholar 

  53. Kurtz A, Wagner C. Role of nitric oxide in the control of renin secretion. Am J Physiol. 1998;275(6 Pt 2):F849–62.

    CAS  PubMed  Google Scholar 

  54. Yanagisawa M, et al. A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature. 1988;332(6163):411–5.

    Article  CAS  PubMed  Google Scholar 

  55. Luscher TF, Seo BG, Buhler FR. Potential role of endothelin in hypertension. Controversy on endothelin in hypertension. Hypertension. 1993;21(6 Pt 1):752–7.

    Article  CAS  PubMed  Google Scholar 

  56. Rabelink TJ, et al. Effects of endothelin-1 on renal function in humans: implications for physiology and pathophysiology. Kidney Int. 1994;46(2):376–81.

    Article  CAS  PubMed  Google Scholar 

  57. Kohan DE. Endothelins in the normal and diseased kidney. Am J Kidney Dis. 1997;29(1):2–26.

    Article  CAS  PubMed  Google Scholar 

  58. Ahn D, et al. Collecting duct-specific knockout of endothelin-1 causes hypertension and sodium retention. J Clin Invest. 2004;114(4):504–11.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  59. Ishikawa T, et al. Positive inotropic action of novel vasoconstrictor peptide endothelin on guinea pig atria. Am J Physiol. 1988;255(4 Pt 2):H970–3.

    CAS  PubMed  Google Scholar 

  60. Schiffrin EL. Vascular endothelin in hypertension. Vascul Pharmacol. 2005;43(1):19–29.

    Article  CAS  PubMed  Google Scholar 

  61. Schiffrin EL. The angiotensin-endothelin relationship: does it play a role in cardiovascular and renal pathophysiology? J Hypertens. 2003;21(12):2245–7.

    Article  CAS  PubMed  Google Scholar 

  62. Gariepy CE, et al. Salt-sensitive hypertension in endothelin-B receptor-deficient rats. J Clin Invest. 2000;105(7):925–33.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  63. Ergul S, et al. Racial differences in plasma endothelin-1 concentrations in individuals with essential hypertension. Hypertension. 1996;28(4):652–5.

    Article  CAS  PubMed  Google Scholar 

  64. Granger JP, et al. Pathophysiology of hypertension during preeclampsia linking placental ischemia with endothelial dysfunction. Hypertension. 2001;38(3 Pt 2):718–22.

    Article  CAS  PubMed  Google Scholar 

  65. Zhou J, et al. Gestational hypoxia induces preeclampsia-like symptoms via heightened endothelin-1 signaling in pregnant rats. Hypertension. 2013;62(3):599–607.

    Article  CAS  PubMed  Google Scholar 

  66. Krum H, et al. The effect of an endothelin-receptor antagonist, bosentan, on blood pressure in patients with essential hypertension. Bosentan Hypertension Investigators. N Engl J Med. 1998;338(12):784–90.

    Article  CAS  PubMed  Google Scholar 

  67. Nakov R, et al. Darusentan: an effective endothelinA receptor antagonist for treatment of hypertension. Am J Hypertens. 2002;15(7 Pt 1):583–9.

    Article  CAS  PubMed  Google Scholar 

  68. Flegal KM, et al. Prevalence of obesity and trends in the distribution of body mass index among US adults, 1999–2010. JAMA. 2012;307(5):491–7.

    Article  PubMed  Google Scholar 

  69. Bretzel RG. Can we further slow down the progression to end-stage renal disease in diabetic hypertensive patients? J Hypertens Suppl. 1997;15(2):S83–8.

    Article  CAS  PubMed  Google Scholar 

  70. Hall JE. The kidney, hypertension, and obesity. Hypertension. 2003;41(3 Pt 2):625–33.

    Article  PubMed  CAS  Google Scholar 

  71. Vogt B, Bochud M, Burnier M. The association of aldosterone with obesity-related hypertension and the metabolic syndrome. Semin Nephrol. 2007;27(5):529–37.

    Article  CAS  PubMed  Google Scholar 

  72. Goodfriend TL, et al. Epoxy-keto derivative of linoleic acid stimulates aldosterone secretion. Hypertension. 2004;43(2):358–63.

    Article  CAS  PubMed  Google Scholar 

  73. da Silva AA, et al. The role of the sympathetic nervous system in obesity-related hypertension. Curr Hypertens Rep. 2009;11(3):206–11.

    Article  PubMed Central  PubMed  Google Scholar 

  74. Schwartz MW, et al. Central nervous system control of food intake. Nature. 2000;404(6778):661–71.

    CAS  PubMed  Google Scholar 

  75. da Silva AA, do Carmo JM, Hall JE. Role of leptin and central nervous system melanocortins in obesity hypertension. Curr Opin Nephrol Hypertens. 2013;22(2):135–40.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  76. Prior LJ, et al. Exposure to a high-fat diet alters leptin sensitivity and elevates renal sympathetic nerve activity and arterial pressure in rabbits. Hypertension. 2010;55(4):862–8.

    Article  CAS  PubMed  Google Scholar 

  77. Mark AL. Selective leptin resistance revisited. Am J Physiol Regul Integr Comp Physiol. 2013;305(6):R566–81.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  78. Wang ZV, Scherer PE. Adiponectin, cardiovascular function, and hypertension. Hypertension. 2008;51(1):8–14.

    Article  CAS  PubMed  Google Scholar 

  79. Ouchi N, et al. Association of hypoadiponectinemia with impaired vasoreactivity. Hypertension. 2003;42(3):231–4.

    Article  CAS  PubMed  Google Scholar 

  80. Tanida M, et al. Effects of adiponectin on the renal sympathetic nerve activity and blood pressure in rats. Exp Biol Med (Maywood). 2007;232(3):390–7.

    CAS  Google Scholar 

  81. Sarafidis PA, Bakris GL. Review: insulin and endothelin: an interplay contributing to hypertension development? J Clin Endocrinol Metab. 2007;92(2):379–85.

    Article  CAS  PubMed  Google Scholar 

  82. Manrique C, Lastra G, Sowers JR. New insights into insulin action and resistance in the vasculature. Ann N Y Acad Sci. 2014;1311:138–50.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  83. de Bold AJ, et al. A rapid and potent natriuretic response to intravenous injection of atrial myocardial extract in rats. Life Sci. 1981;28(1):89–94.

    Article  PubMed  Google Scholar 

  84. Iida T, et al. Brain natriuretic peptide is cosecreted with atrial natriuretic peptide from porcine cardiocytes. FEBS Lett. 1990;260(1):98–100.

    Article  CAS  PubMed  Google Scholar 

  85. Nakao K, et al. Molecular biology and biochemistry of the natriuretic peptide system. I: natriuretic peptides. J Hypertens. 1992;10(9):907–12.

    Article  CAS  PubMed  Google Scholar 

  86. Kario K, et al. Efficacy and safety of LCZ696, a first-in-class angiotensin receptor neprilysin inhibitor, in Asian patients with hypertension: a randomized, double-blind, placebo-controlled study. Hypertension. 2014;63(4):698–705.

    Article  CAS  PubMed  Google Scholar 

  87. Fluckiger JP, et al. Effect of atriopeptin III on hematocrit and volemia of nephrectomized rats. Am J Physiol. 1986;251(4 Pt 2):H880–3.

    CAS  PubMed  Google Scholar 

  88. Volpe M, et al. Effect of atrial natriuretic factor on blood pressure, renin, and aldosterone in Goldblatt hypertension. Hypertension. 1985;7(3 Pt 2):I43–8.

    Article  CAS  PubMed  Google Scholar 

  89. de Wardener HE. The hypothalamus and hypertension. Physiol Rev. 2001;81(4):1599–658.

    PubMed  Google Scholar 

  90. John SW, et al. Genetic decreases in atrial natriuretic peptide and salt-sensitive hypertension. Science. 1995;267(5198):679–81.

    Article  CAS  PubMed  Google Scholar 

  91. Lopez MJ, et al. Salt-resistant hypertension in mice lacking the guanylyl cyclase-A receptor for atrial natriuretic peptide. Nature. 1995;378(6552):65–8.

    Article  CAS  PubMed  Google Scholar 

  92. Steinhelper ME, Cochrane KL, Field LJ. Hypotension in transgenic mice expressing atrial natriuretic factor fusion genes. Hypertension. 1990;16(3):301–7.

    Article  CAS  PubMed  Google Scholar 

  93. Jin HK, et al. Impaired release of atrial natriuretic factor in NaCl-loaded spontaneously hypertensive rats. Hypertension. 1988;11(6 Pt 2):739–44.

    Article  CAS  PubMed  Google Scholar 

  94. Schiffrin EL, St-Louis J, Essiambre R. Platelet binding sites and plasma concentration of atrial natriuretic peptide in patients with essential hypertension. J Hypertens. 1988;6(7):565–72.

    Article  CAS  PubMed  Google Scholar 

  95. Talartschik J, et al. Low atrial natriuretic peptide plasma concentrations in 100 patients with essential hypertension. Am J Hypertens. 1990;3(1):45–7.

    CAS  PubMed  Google Scholar 

  96. Ferrari P, et al. Dysregulation of atrial natriuretic factor in hypertension-prone man. J Clin Endocrinol Metab. 1990;71(4):944–51.

    Article  CAS  PubMed  Google Scholar 

  97. Campese VM, et al. Salt intake and plasma atrial natriuretic peptide and nitric oxide in hypertension. Hypertension. 1996;28(3):335–40.

    Article  CAS  PubMed  Google Scholar 

  98. Cannone V, et al. Atrial natriuretic peptide genetic variant rs5065 and risk for cardiovascular disease in the general community: a 9-year follow-up study. Hypertension. 2013;62(5):860–5.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  99. Rubattu S, Sciarretta S, Volpe M. Atrial natriuretic peptide gene variants and circulating levels: implications in cardiovascular diseases. Clin Sci (Lond). 2014;127(1):1–13.

    Article  CAS  Google Scholar 

  100. Margolius HS, et al. Urinary kallikrein excretion in hypertension. Circ Res. 1972;31 Suppl 2:125–31.

    PubMed  Google Scholar 

  101. Levy SB, et al. Urinary kallikrein and plasma renin activity as determinants of renal blood flow. The influence of race and dietary sodium intake. J Clin Invest. 1977;60(1):129–38.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  102. Alfie ME, et al. Effect of high salt intake in mutant mice lacking bradykinin-B2 receptors. Hypertension. 1997;29(1 Pt 2):483–7.

    Article  CAS  PubMed  Google Scholar 

  103. Majima M, et al. High sensitivity to salt in kininogen-deficient brown Norway Katholiek rats. Hypertension. 1993;22(5):705–14.

    Article  CAS  PubMed  Google Scholar 

  104. Madeddu P, et al. Chronic kinin receptor blockade induces hypertension in deoxycorticosterone-treated rats. Br J Pharmacol. 1993;108(3):651–7.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  105. Wang J, et al. Human tissue kallikrein induces hypotension in transgenic mice. Hypertension. 1994;23(2):236–43.

    Article  CAS  PubMed  Google Scholar 

  106. Berry TD, et al. A gene for high urinary kallikrein may protect against hypertension in Utah kindreds. Hypertension. 1989;13(1):3–8.

    Article  CAS  PubMed  Google Scholar 

  107. Zinner SH, et al. Familial aggregation of urinary kallikrein concentration in childhood: relation to blood pressure, race and urinary electrolytes. Am J Epidemiol. 1976;104(2):124–32.

    CAS  PubMed  Google Scholar 

  108. Katori M, Majima M. Renal (tissue) kallikrein-kinin system in the kidney and novel potential drugs for salt-sensitive hypertension. Prog Drug Res. 2014;69:59–109.

    PubMed  Google Scholar 

  109. Share L. Role of vasopressin in cardiovascular regulation. Physiol Rev. 1988;68(4):1248–84.

    CAS  PubMed  Google Scholar 

  110. Bankir L, Bouby N, Ritz E. Vasopressin: a novel target for the prevention and retardation of kidney disease? Nat Rev Nephrol. 2013;9(4):223–39.

    Article  CAS  PubMed  Google Scholar 

  111. Okada H, et al. Chronic and selective vasopressin blockade in spontaneously hypertensive rats. Am J Physiol. 1994;267(6 Pt 2):R1467–71.

    CAS  PubMed  Google Scholar 

  112. Burrell LM, et al. Blood pressure-lowering effect of an orally active vasopressin V1 receptor antagonist in mineralocorticoid hypertension in the rat. Hypertension. 1994;23(6 Pt 1):737–43.

    Article  CAS  PubMed  Google Scholar 

  113. Burrell LM, et al. Age-dependent regulation of renal vasopressin V(1A) and V(2) receptors in rats with genetic hypertension: implications for the treatment of hypertension. J Am Soc Hypertens. 2013;7(1):3–13.

    Article  CAS  PubMed  Google Scholar 

  114. Naitoh M, et al. Modulation of genetic hypertension by short-term AVP V1A or V2 receptor antagonism in young SHR. Am J Physiol. 1997;272(2 Pt 2):F229–34.

    CAS  PubMed  Google Scholar 

  115. Weber R, et al. Effects of SR 49059, a new orally active and specific vasopressin V1 receptor antagonist, on vasopressin-induced vasoconstriction in humans. Hypertension. 1997;30(5):1121–7.

    Article  CAS  PubMed  Google Scholar 

  116. Thibonnier M, et al. Effects of the nonpeptide V(1) vasopressin receptor antagonist SR49059 in hypertensive patients. Hypertension. 1999;34(6):1293–300.

    Article  CAS  PubMed  Google Scholar 

  117. Gavras H, et al. Effects of a specific inhibitor of the vascular action of vasopressin in humans. Hypertension. 1984;6(2 Pt 2):I156–60.

    Article  CAS  PubMed  Google Scholar 

  118. Gavras H. Role of vasopressin in clinical hypertension and congestive cardiac failure: interaction with the sympathetic nervous system. Clin Chem. 1991;37(10 Pt 2):1828–30.

    CAS  PubMed  Google Scholar 

  119. Harris RC. Abnormalities in renal dopamine signaling and hypertension: the role of GRK4. Curr Opin Nephrol Hypertens. 2012;21(1):61–5.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  120. Felder RA, Jose PA. Mechanisms of disease: the role of GRK4 in the etiology of essential hypertension and salt sensitivity. Nat Clin Pract Nephrol. 2006;2(11):637–50.

    Article  CAS  PubMed  Google Scholar 

  121. Svendsen UG. The importance of thymus in the pathogenesis of the chronic phase of hypertension in mice following partial infarction of the kidney. Acta Pathol Microbiol Scand A. 1977;85(4):539–47.

    CAS  PubMed  Google Scholar 

  122. Bataillard A, et al. Antihypertensive effect of neonatal thymectomy in the genetically hypertensive LH rat. Thymus. 1986;8(6):321–30.

    CAS  PubMed  Google Scholar 

  123. Idris-Khodja N, et al. Dual opposing roles of adaptive immunity in hypertension. Eur Heart J. 2014;35(19):1238–44.

    Article  CAS  PubMed  Google Scholar 

  124. Harrison DG, et al. Inflammation, immunity, and hypertension. Hypertension. 2011;57(2):132–40.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  125. Cheng S, et al. Blood pressure tracking over the adult life course: patterns and correlates in the Framingham heart study. Hypertension. 2012;60(6):1393–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  126. Burt VL, et al. Prevalence of hypertension in the US adult population. Results from the Third National Health and Nutrition Examination Survey, 1988–1991. Hypertension. 1995;25(3):305–13.

    Article  CAS  PubMed  Google Scholar 

  127. Bubb KJ, Khambata RS, Ahluwalia A. Sexual dimorphism in rodent models of hypertension and atherosclerosis. Br J Pharmacol. 2012;167(2):298–312.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  128. Reckelhoff JF. Gender differences in the regulation of blood pressure. Hypertension. 2001;37(5):1199–208.

    Article  CAS  PubMed  Google Scholar 

  129. Charchar FJ, et al. Y is there a risk to being male? Trends Endocrinol Metab. 2003;14(4):163–8.

    Article  CAS  PubMed  Google Scholar 

  130. Reckelhoff JF, Zhang H, Granger JP. Testosterone exacerbates hypertension and reduces pressure-natriuresis in male spontaneously hypertensive rats. Hypertension. 1998;31(1 Pt 2):435–9.

    Article  CAS  PubMed  Google Scholar 

  131. Baltatu O, et al. Abolition of end-organ damage by antiandrogen treatment in female hypertensive transgenic rats. Hypertension. 2003;41(3 Pt 2):830–3.

    Article  CAS  PubMed  Google Scholar 

  132. Quan A, et al. Androgens augment proximal tubule transport. Am J Physiol Renal Physiol. 2004;287(3):F452–9.

    Article  CAS  PubMed  Google Scholar 

  133. Quinkler M, et al. Androgen receptor-mediated regulation of the alpha-subunit of the epithelial sodium channel in human kidney. Hypertension. 2005;46(4):787–98.

    Article  CAS  PubMed  Google Scholar 

  134. Dahl LK, et al. Role of the gonads in hypertension-prone rats. J Exp Med. 1975;142(3):748–59.

    Article  CAS  PubMed  Google Scholar 

  135. Masubuchi Y, et al. Gonadectomy-induced reduction of blood pressure in adult spontaneously hypertensive rats. Acta Endocrinol (Copenh). 1982;101(1):154–60.

    CAS  Google Scholar 

  136. Chappell MC, Yamaleyeva LM, Westwood BM. Estrogen and salt sensitivity in the female mRen(2). Lewis rat. Am J Physiol Regul Integr Comp Physiol. 2006;291(5):R1557–63.

    Article  CAS  PubMed  Google Scholar 

  137. Kang AK, Miller JA. Impact of gender on renal disease: the role of the renin angiotensin system. Clin Invest Med. 2003;26(1):38–44.

    CAS  PubMed  Google Scholar 

  138. James GD, et al. Renin relationship to sex, race and age in a normotensive population. J Hypertens Suppl. 1986;4(5):S387–9.

    CAS  PubMed  Google Scholar 

  139. Hollenberg NK, et al. Renal blood flow and its response to angiotensin II. An interaction between oral contraceptive agents, sodium intake, and the renin-angiotensin system in healthy young women. Circ Res. 1976;38(1):35–40.

    Article  CAS  PubMed  Google Scholar 

  140. Ellison KE, et al. Androgen regulation of rat renal angiotensinogen messenger RNA expression. J Clin Invest. 1989;83(6):1941–5.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  141. Katz FH, Roper EF. Testosterone effect on renin system in rats. Proc Soc Exp Biol Med. 1977;155(3):330–3.

    Article  CAS  PubMed  Google Scholar 

  142. Chen YF, Naftilan AJ, Oparil S. Androgen-dependent angiotensinogen and renin messenger RNA expression in hypertensive rats. Hypertension. 1992;19(5):456–63.

    Article  CAS  PubMed  Google Scholar 

  143. Leung PS, et al. Androgen dependent expression of AT1 receptor and its regulation of anion secretion in rat epididymis. Cell Biol Int. 2002;26(1):117–22.

    Article  CAS  PubMed  Google Scholar 

  144. Miller JA, Anacta LA, Cattran DC. Impact of gender on the renal response to angiotensin II. Kidney Int. 1999;55(1):278–85.

    Article  CAS  PubMed  Google Scholar 

  145. Pechere-Bertschi A, Burnier M. Female sex hormones, salt, and blood pressure regulation. Am J Hypertens. 2004;17(10):994–1001.

    Article  CAS  PubMed  Google Scholar 

  146. Chobanian AV. Clinical practice. Isolated systolic hypertension in the elderly. N Engl J Med. 2007;357(8):789–96.

    Article  CAS  PubMed  Google Scholar 

  147. Lehoux S, et al. Pressure-induced matrix metalloproteinase-9 contributes to early hypertensive remodeling. Circulation. 2004;109(8):1041–7.

    Article  CAS  PubMed  Google Scholar 

  148. Dhingra R, et al. Relations of matrix remodeling biomarkers to blood pressure progression and incidence of hypertension in the community. Circulation. 2009;119(8):1101–7.

    Article  PubMed Central  PubMed  Google Scholar 

  149. Nagareddy PR, et al. Inhibition of matrix metalloproteinase-2 improves endothelial function and prevents hypertension in insulin-resistant rats. Br J Pharmacol. 2012;165(3):705–15.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  150. Jensky NE, et al. Blood pressure and vascular calcification. Hypertension. 2010;55(4):990–7.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  151. Mente A, et al. Association of urinary sodium and potassium excretion with blood pressure. N Engl J Med. 2014;371(7):601–11.

    Article  PubMed  CAS  Google Scholar 

  152. Elliott P, et al. The INTERSALT study: main results, conclusions and some implications. Clin Exp Hypertens A. 1989;11(5–6):1025–34.

    Article  CAS  PubMed  Google Scholar 

  153. Chiolero A, Wurzner G, Burnier M. Renal determinants of the salt sensitivity of blood pressure. Nephrol Dial Transplant. 2001;16(3):452–8.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Service of Nephrology and Hypertension, Department of Medicine, Centre Hospitalier Universitaire Vaudois (CHUV), Rue du Bugnon 17, Lausanne, 1011, Switzerland

    Michel Burnier MD & Grégoire Wuerzner MD

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  1. Michel Burnier MD
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  2. Grégoire Wuerzner MD
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Correspondence to Michel Burnier MD .

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Editors and Affiliations

  1. Center for Drug Evaluation and Research Division of Cardiovascular and Renal Products, US Food and Drug Administration, Silver Spring, Maryland, USA

    Gowraganahalli Jagadeesh

  2. Pharmacology Unit, AIMST University, Bedong, Malaysia

    Pitchai Balakumar

  3. Center for Drug Evaluation and Research Division of Cardiovascular and Renal Products, US Food and Drug Administration, Silver Spring, Maryland, USA

    Khin Maung-U

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Burnier, M., Wuerzner, G. (2015). Pathophysiology of Hypertension. In: Jagadeesh, G., Balakumar, P., Maung-U, K. (eds) Pathophysiology and Pharmacotherapy of Cardiovascular Disease. Adis, Cham. https://doi.org/10.1007/978-3-319-15961-4_31

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  • DOI: https://doi.org/10.1007/978-3-319-15961-4_31

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