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  • Review Article
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The role of the kidney in regulating arterial blood pressure

Nature Reviews Nephrology volume 8, pages 602–609 (2012)Cite this article

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Abstract

The kidney plays a central role in the regulation of arterial blood pressure. A large body of experimental and physiological evidence indicates that renal control of extracellular volume and renal perfusion pressure are closely involved in maintaining the arterial circulation and blood pressure. Renal artery perfusion pressure directly regulates sodium excretion—a process known as pressure natriuresis—and influences the activity of various vasoactive systems such as the renin–angiotensin–aldosterone system. As a result, many researchers argue that identifying any marked rise in blood pressure requires resetting of the relationship between arterial blood pressure and urinary sodium excretion, which can occur by an array of systemic or local mechanisms. Almost all of the monogenic forms of hypertension affect sites in the kidney associated with sodium handling and transport. Experimental models of spontaneous hypertension, such as the Dahl salt-sensitive rat, have been used to study the effects of kidney transplantation on blood pressure. Results from studies of kidney transplantation indicate that pressure sensitivity to sodium intake 'follows' the kidney, meaning that the recipient of a 'salt-resistant kidney' acquires sodium resistance, and that the recipient of a 'salt-sensitive kidney' acquires pressure sensitivity. The examples above and discussed in this Review demonstrate that it should come as no surprise that most disorders that affect the kidney or the renal vasculature commonly lead to secondary forms of hypertension.

Key Points

  • Renal artery perfusion pressure directly regulates sodium excretion, a process known as pressure natriuresis

  • The renin–angiotensin–aldosterone system has a central role in maintaining the pressure–natriuresis relationship

  • Maladaptive changes in tubular sodium and chloride handling leads to arterial hypertension despite the presence of a normal glomerular filtration rate

  • Rare inherited forms of hypertension involve gain or loss of function mutations in a single gene and are associated with increased sodium reabsorption in the distal nephron

  • Reduced nephron number contributes to the development of hypertension

  • The kidney is the origin of afferent sympathetic signalling that modulates the sympathetic nervous system, the activity of which increases in patients with renal failure

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Figure 1: Prevalence of high blood pressure by level of GFR.
Figure 2: Relationship between arterial blood pressure and angiotensin II production at various levels of sodium intake.

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References

  1. Kearney, P. M. et al. Global burden of hypertension: analysis of worldwide data. Lancet 365, 217–223 (2005).

    Article  PubMed  Google Scholar 

  2. Udani, S., Lazich, I. & Bakris, G. L. Epidemiology of hypertensive kidney disease. Nat. Rev. Nephrol. 7, 11–21 (2011).

    Article  PubMed  Google Scholar 

  3. US Renal Data System. 2011 Annual Data Report [online], (2011).

  4. Josephson, S., Lännergren, K. & Eklöf, A. C. Partial ureteric obstruction in weanling rats. II. Long-term effects on renal function and arterial blood pressure. Urol. Int. 48, 384–390 (1992).

    Article  CAS  PubMed  Google Scholar 

  5. Bianchi, G., Fox, U., Di Francesco, G. F., Giovanetti, A. M. & Pagetti, D. Blood pressure changes produced by kidney cross-transplantation between spontaneously hypertensive rats and normotensive rats. Clin. Sci. Mol. Med. 47, 435–448 (1974).

    CAS  PubMed  Google Scholar 

  6. Patschan, O., Kuttler, B., Heemann, U., Uber, A. & Rettig, R. Kidneys from normotensive donors lower blood pressure in young transplanted spontaneously hypertensive rats. Am. J. Physiol. 273, R175–R180 (1997).

    CAS  PubMed  Google Scholar 

  7. Guidi, E. et al. Hypertension may be transplanted with the kidney in humans: a long-term historical prospective follow-up of recipients grafted with kidneys coming from donors with or without hypertension in their families. J. Am. Soc. Nephrol. 7, 1131–1138 (1996).

    CAS  PubMed  Google Scholar 

  8. Chun, T. Y. et al. Ethnic differences in renal responses to furosemide. Hypertension 52, 241–248 (2008).

    Article  CAS  PubMed  Google Scholar 

  9. Guerrot, D. et al. Reduced insulin secretion and nocturnal dipping of blood pressure are associated with a disturbed circadian pattern of urine excretion in metabolic syndrome. J. Clin. Endocrinol. Metab. 96, E929–E933 (2011).

    Article  CAS  PubMed  Google Scholar 

  10. Burnier, M. Alterations of renal sodium handling in arterial hypertension. Curr. Hypertens. Rep. 10, 85–86 (2008).

    Article  PubMed  Google Scholar 

  11. Sinclair, A. M. et al. Secondary hypertension in a blood pressure clinic. Arch. Intern. Med. 147, 1289–1293 (1987).

    Article  CAS  PubMed  Google Scholar 

  12. National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am. J. Kidney Dis. 39 (Suppl. 1), S1–S266 (2002).

  13. Sarafidis, P. A. et al. Hypertension awareness, treatment, and control in chronic kidney disease. Am. J. Med. 121, 332–340 (2008).

    Article  PubMed  Google Scholar 

  14. Plantinga, L. C. et al. Blood pressure control among persons without and with chronic kidney disease: US trends and risk factors 1999–2006. Hypertension 54, 47–56 (2009).

    Article  CAS  PubMed  Google Scholar 

  15. Guyton, A. C. Renal function curves and control of body fluids and arterial pressure. Acta Physiol. Scand. Suppl. 591, 107–113 (1990).

    CAS  PubMed  Google Scholar 

  16. Guyton, A. C. Physiologic regulation of arterial pressure. Am. J. Cardiol. 8, 401–407 (1961).

    Article  CAS  PubMed  Google Scholar 

  17. Wang, C. T., Chin, S. Y. & Navar, L. G. Impairment of pressure-natriuresis and renal autoregulation in ANG II-infused hypertensive rats. Am. J. Physiol. Renal Physiol. 279, F319–F325 (2000).

    Article  CAS  PubMed  Google Scholar 

  18. Suckling, R. J., He, F. J., Markandu, N. D. & MacGregor, G. A. Dietary salt influences postprandial plasma sodium concentration and systolic blood pressure. Kidney Int. 81, 407–411 (2012).

    Article  CAS  PubMed  Google Scholar 

  19. Kawasaki, T., Delea, C. S., Bartter, F. C. & Smith, H. The effect of high-sodium and low-sodium intakes on blood pressure and other related variables in human subjects with idiopathic hypertension. Am. J. Med. 64, 193–198 (1978).

    Article  CAS  PubMed  Google Scholar 

  20. Weinberger, M. H. Sodium sensitivity of blood pressure. Curr. Opin. Nephrol. Hypertens. 2, 935–939 (1993).

    Article  CAS  PubMed  Google Scholar 

  21. Weinberger, M. H., Miller, J. Z., Luft, F. C., Grim, C. E. & Fineberg, N. S. Definitions and characteristics of sodium sensitivity and blood pressure resistance. Hypertension 8, II127–II134 (1986).

    Article  CAS  PubMed  Google Scholar 

  22. Chiolero, A., Maillard, M., Nussberger, J., Brunner, H. R. & Burnier, M. Proximal sodium reabsorption: an independent determinant of blood pressure response to salt. Hypertension 36, 631–637 (2000).

    Article  CAS  PubMed  Google Scholar 

  23. Fujii, T. et al. Circadian rhythm of natriuresis is disturbed in nondipper type of essential hypertension. Am. J. Kidney Dis. 33, 29–35 (1999).

    Article  CAS  PubMed  Google Scholar 

  24. Uzu, T. et al. High sodium sensitivity implicates nocturnal hypertension in essential hypertension. Hypertension 28, 139–142 (1996).

    Article  CAS  PubMed  Google Scholar 

  25. Fuenmayor, N., Moreira, E. & Cubeddu, L. X. Salt sensitivity is associated with insulin resistance in essential hypertension. Am. J. Hypertens. 11, 397–402 (1998).

    Article  CAS  PubMed  Google Scholar 

  26. Galletti, F. et al. NaCl sensitivity of essential hypertensive patients is related to insulin resistance. J. Hypertens. 15, 1485–1491 (1997).

    Article  CAS  PubMed  Google Scholar 

  27. Yatabe, M. S. et al. Salt sensitivity is associated with insulin resistance, sympathetic overactivity, and decreased suppression of circulating renin activity in lean patients with essential hypertension. Am. J. Clin. Nutr. 92, 77–82 (2010).

    Article  CAS  PubMed  Google Scholar 

  28. Bigazzi, R. et al. Microalbuminuria in salt-sensitive patients. A marker for renal and cardiovascular risk factors. Hypertension 23, 195–199 (1994).

    Article  CAS  PubMed  Google Scholar 

  29. de la Sierra, A. et al. Increased left ventricular mass in salt-sensitive hypertensive patients. J. Hum. Hypertens. 10, 795–799 (1996).

    CAS  PubMed  Google Scholar 

  30. Biollaz, J., Waeber, B., Diezi, J., Burnier, M. & Brunner, H. R. Lithium infusion to study sodium handling in unanesthetized hypertensive rats. Hypertension 8, 117–121 (1986).

    Article  CAS  PubMed  Google Scholar 

  31. Burnier, M., Biollaz, J., Magnin, J. L., Bidlingmeyer, M. & Brunner, H. R. Renal sodium handling in patients with untreated hypertension and white coat hypertension. Hypertension 23, 496–502 (1994).

    Article  CAS  PubMed  Google Scholar 

  32. Barba, G. et al. Renal function and blood pressure response to dietary salt restriction in normotensive men. Hypertension 27, 1160–1164 (1996).

    Article  CAS  PubMed  Google Scholar 

  33. Machnik, A. et al. Macrophages regulate salt-dependent volume and blood pressure by a vascular endothelial growth factor-C-dependent buffering mechanism. Nat. Med. 15, 545–552 (2009).

    Article  CAS  PubMed  Google Scholar 

  34. Burnier, M. Sodium balance and hypertension: rare genetic disorders expose pathogenic mechanisms. Exp. Nephrol. 6, 496–501 (1998).

    Article  CAS  PubMed  Google Scholar 

  35. Chiolero, A., Würzner, G. & Burnier, M. Renal determinants of the salt sensitivity of blood pressure. Nephrol. Dial. Transplant. 16, 452–458 (2001).

    Article  CAS  PubMed  Google Scholar 

  36. Boer, P. A., Morelli, J. M., Figueiredo, J. F. & Gontijo, J. A. Early altered renal sodium handling determined by lithium clearance in spontaneously hypertensive rats (SHR): role of renal nerves. Life Sci. 76, 1805–1815 (2005).

    Article  CAS  PubMed  Google Scholar 

  37. Cusi, D. et al. Polymorphisms of α-adducin and salt sensitivity in patients with essential hypertension. Lancet 349, 1353–1357 (1997).

    Article  CAS  PubMed  Google Scholar 

  38. Tripodi, G. et al. Hypertension-associated point mutations in the adducin alpha and beta subunits affect actin cytoskeleton and ion transport. J. Clin. Invest. 97, 2815–2822 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Poch, E. et al. Molecular basis of salt sensitivity in human hypertension. Evaluation of renin-angiotensin-aldosterone system gene polymorphisms. Hypertension 38, 1204–1209 (2001).

    Article  CAS  PubMed  Google Scholar 

  40. Kidambi, S. et al. Non-replication study of a genome-wide association study for hypertension and blood pressure in African Americans. BMC Med. Genet. 13, 27 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Toka, H. R. & Luft, F. C. Monogenic forms of human hypertension. Semin. Nephrol. 22, 81–88 (2002).

    Article  CAS  PubMed  Google Scholar 

  42. Ji, W. et al. Rare independent mutations in renal salt handling genes contribute to blood pressure variation. Nat. Genet. 40, 592–599 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Wilson, F. H. et al. Molecular pathogenesis of inherited hypertension with hyperkalemia: the Na-Cl cotransporter is inhibited by wild-type but not mutant WNK4. Proc. Natl Acad. Sci. USA 100, 680–684 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Lifton, R. P. et al. Hereditary hypertension caused by chimaeric gene duplications and ectopic expression of aldosterone synthase. Nat. Genet. 2, 66–74 (1992).

    Article  CAS  PubMed  Google Scholar 

  45. Ritz, E., Amann, K., Koleganova, N. & Benz, K. Prenatal programming—effects on blood pressure and renal function. Nat. Rev. Nephrol. 7, 137–144 (2011).

    Article  PubMed  Google Scholar 

  46. Hoy, W. E., Hughson, M. D., Bertram, J. F., Douglas-Denton, R. & Amann, K. Nephron number, hypertension, renal disease, and renal failure. J. Am. Soc. Nephrol. 16, 2557–2564 (2005).

    Article  PubMed  Google Scholar 

  47. Hughson, M. D., Douglas-Denton, R., Bertram, J. F. & Hoy, W. E. Hypertension, glomerular number, and birth weight in African Americans and white subjects in the southeastern United States. Kidney Int. 69, 671–678 (2006).

    Article  CAS  PubMed  Google Scholar 

  48. Nyengaard, J. R. & Bendtsen, T. F. Glomerular number and size in relation to age, kidney weight, and body surface in normal man. Anat. Rec. 232, 194–201 (1992).

    Article  CAS  PubMed  Google Scholar 

  49. Brenner, B. M. & Chertow, G. M. Congenital oligonephropathy and the etiology of adult hypertension and progressive renal injury. Am. J. Kidney Dis. 23, 171–175 (1994).

    Article  CAS  PubMed  Google Scholar 

  50. Hoy, W. E., Hughson, M. D., Singh, G. R., Douglas-Denton, R. & Bertram, J. F. Reduced nephron number and glomerulomegaly in Australian Aborigines: a group at high risk for renal disease and hypertension. Kidney Int. 70, 104–110 (2006).

    Article  CAS  PubMed  Google Scholar 

  51. Keller, G., Zimmer, G., Mall, G., Ritz, E. & Amann, K. Nephron number in patients with primary hypertension. N. Engl. J. Med. 348, 101–108 (2003).

    Article  PubMed  Google Scholar 

  52. Zimanyi, M. A. et al. Nephron number and individual glomerular volumes in male Caucasian and African American subjects. Nephrol. Dial. Transplant. 24, 2428–2433 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  53. Rule, A. D. et al. Association of kidney function and metabolic risk factors with density of glomeruli on renal biopsy samples from living donors. Mayo Clin. Proc. 86, 282–290 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  54. Textor, S. C. et al. Association of filtered sodium load with medullary volumes and medullary hypoxia in hypertensive African Americans as compared with whites. Am. J. Kidney Dis. 59, 229–237 (2012).

    Article  CAS  PubMed  Google Scholar 

  55. Aviv, A., Hollenberg, N. K. & Weder, A. B. Sodium glomerulopathy: tubuloglomerular feedback and renal injury in African Americans. Kidney Int. 65, 361–368 (2004).

    Article  PubMed  Google Scholar 

  56. Genovese, G. et al. Association of trypanolytic ApoL1 variants with kidney disease in African Americans. Science 329, 841–845 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Esler, M., Lambert, E. & Schlaich, M. Point: Chronic activation of the sympathetic nervous system is the dominant contributor to systemic hypertension. J. Appl. Physiol. 109, 1996–1998 (2010).

    Article  PubMed  Google Scholar 

  58. Mark, A. L. The sympathetic nervous system in hypertension: a potential long-term regulator of arterial pressure. J. Hypertens. Suppl. 14, S159–S165 (1996).

    CAS  PubMed  Google Scholar 

  59. DiBona, G. F. Physiology in perspective: the wisdom of the body. Neural control of the kidney. Am. J. Physiol. Regul. Integr. Comp. Physiol. 289, R633–R641 (2005).

    Article  CAS  PubMed  Google Scholar 

  60. Rafiq, K. et al. Renal sympathetic denervation suppresses de novo podocyte injury and albuminuria in rats with aortic regurgitation. Circulation 125, 1402–1413 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Calaresu, F. R. & Ciriello, J. Renal afferent nerves affect discharge rate of medullary and hypothalamic single units in the cat. J. Auton. Nerv. Syst. 3, 311–320 (1981).

    Article  CAS  PubMed  Google Scholar 

  62. Ciriello, J. & Calaresu, F. R. Hypothalamic projections of renal afferent nerves in the cat. Can. J. Physiol. Pharmacol. 58, 574–576 (1980).

    Article  CAS  PubMed  Google Scholar 

  63. Katholi, R. E., Rocha-Singh, K. J., Goswami, N. J. & Sobotka, P. A. Renal nerves in the maintenance of hypertension: a potential therapeutic target. Curr. Hypertens. Rep. 12, 196–204 (2010).

    Article  PubMed  Google Scholar 

  64. Ye, S., Ozgur, B. & Campese, V. M. Renal afferent impulses, the posterior hypothalamus, and hypertension in rats with chronic renal failure. Kidney Int. 51, 722–727 (1997).

    Article  CAS  PubMed  Google Scholar 

  65. Converse, R. L. Jr et al. Sympathetic overactivity in patients with chronic renal failure. N. Engl. J. Med. 327, 1912–1918 (1992).

    Article  PubMed  Google Scholar 

  66. Ecder, T. & Schrier, R. W. Hypertension in autosomal-dominant polycystic kidney disease: early occurrence and unique aspects. J. Am. Soc. Nephrol. 12, 194–200 (2001).

    CAS  PubMed  Google Scholar 

  67. Gabow, P. A. et al. Renal structure and hypertension in autosomal dominant polycystic kidney disease. Kidney Int. 38, 1177–1180 (1990).

    Article  CAS  PubMed  Google Scholar 

  68. Klein, I. H., Ligtenberg, G., Oey, P. L., Koomans, H. A. & Blankestijn, P. J. Sympathetic activity is increased in polycystic kidney disease and is associated with hypertension. J. Am. Soc. Nephrol. 12, 2427–2433 (2001).

    CAS  PubMed  Google Scholar 

  69. Esler, M. D. et al. Renal sympathetic denervation in patients with treatment-resistant hypertension (The Symplicity HTN-2 Trial): a randomised controlled trial. Lancet 376, 1903–1909 (2010).

    Article  PubMed  Google Scholar 

  70. Witkowski, A. et al. Effects of renal sympathetic denervation on blood pressure, sleep apnea course, and glycemic control in patients with resistant hypertension and sleep apnea. Hypertension 58, 559–565 (2011).

    Article  CAS  PubMed  Google Scholar 

  71. Simões E Silva, A. C. & Flynn, J. T. The renin-angiotensin-aldosterone system in 2011: role in hypertension and chronic kidney disease. Pediatr. Nephrol. http://dx.doi.org/10.1007/s00467-011-2002-y.

  72. Bhave, G. & Neilson, E. G. Body fluid dynamics: back to the future. J. Am. Soc. Nephrol. 22, 2166–2181 (2011).

    Article  CAS  PubMed  Google Scholar 

  73. Graham, P. C. & Lindop, G. B. The anatomy of the renin-secreting cell in adult polycystic kidney disease. Kidney Int. 33, 1084–1090 (1988).

    Article  CAS  PubMed  Google Scholar 

  74. Torres, V. E. et al. Synthesis of renin by tubulocystic epithelium in autosomal-dominant polycystic kidney disease. Kidney Int. 42, 364–373 (1992).

    Article  CAS  PubMed  Google Scholar 

  75. Wang, E., Yayama, K., Takano, M. & Okamoto, H. Sexual dimorphism of urine angiotensinogen excretion in the rat. Jpn J. Pharmacol. 64, 243–250 (1994).

    Article  CAS  PubMed  Google Scholar 

  76. Ingelfinger, J. R., Pratt, R. E., Ellison, K. & Dzau, V. J. Sodium regulation of angiotensinogen mRNA expression in rat kidney cortex and medulla. J. Clin. Invest. 78, 1311–1315 (1986).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Lalouel, J. M. & Rohrwasser, A. Genetic susceptibility to essential hypertension: insight from angiotensinogen. Hypertension 49, 597–603 (2007).

    Article  CAS  PubMed  Google Scholar 

  78. Thethi, T., Kamiyama, M. & Kobori, H. The link between the renin-angiotensin-aldosterone system and renal injury in obesity and the metabolic syndrome. Curr. Hypertens. Rep. 14, 160–169 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Kang, J. J. et al. The collecting duct is the major source of prorenin in diabetes. Hypertension 51, 1597–1604 (2008).

    Article  CAS  PubMed  Google Scholar 

  80. Xue, C. & Siragy, H. M. Local renal aldosterone system and its regulation by salt, diabetes, and angiotensin II type 1 receptor. Hypertension 46, 584–590 (2005).

    Article  CAS  PubMed  Google Scholar 

  81. Kobori, H., Harrison-Bernard, L. M. & Navar, L. G. Expression of angiotensinogen mRNA and protein in angiotensin II-dependent hypertension. J. Am. Soc. Nephrol. 12, 431–439 (2001).

    CAS  PubMed  Google Scholar 

  82. Kobori, H., Nishiyama, A., Harrison-Bernard, L. M. & Navar, L. G. Urinary angiotensinogen as an indicator of intrarenal angiotensin status in hypertension. Hypertension 41, 42–49 (2003).

    Article  CAS  PubMed  Google Scholar 

  83. Jang, H. R. et al. The origin and the clinical significance of urinary angiotensinogen in proteinuric IgA nephropathy patients. Ann. Med. 44, 448–457 (2012).

    Article  CAS  PubMed  Google Scholar 

  84. Prieto-Carrasquero, M. C. et al. Enhancement of collecting duct renin in angiotensin II-dependent hypertensive rats. Hypertension 44, 223–229 (2004).

    Article  CAS  PubMed  Google Scholar 

  85. Gilbert, R. E. et al. Pathological expression of renin and angiotensin II in the renal tubule after subtotal nephrectomy. Implications for the pathogenesis of tubulointerstitial fibrosis. Am. J. Pathol. 155, 429–440 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Huang, L., Howard, C. G. & Mitchell, K. D. Chronic direct renin inhibition with aliskiren prevents the development of hypertension in Cyp1a1-Ren2 transgenic rats with inducible ANG II-dependent hypertension. Am. J. Med. Sci. http://dx.doi.org/10.1097/MAJ.0b013e3182410d1e.

  87. Howard, C. G. & Mitchell, K. D. Renal functional responses to selective intrarenal renin inhibition in Cyp1a1-Ren2 transgenic rats with ANG II-dependent malignant hypertension. Am. J. Physiol. Renal Physiol. 302, F52–F59 (2012).

    Article  CAS  PubMed  Google Scholar 

  88. Navar, L. G., Prieto, M. C., Satou, R. & Kobori, H. Intrarenal angiotensin II and its contribution to the genesis of chronic hypertension. Curr. Opin. Pharmacol. 11, 180–186 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Kobori, H., Nangaku, M., Navar, L. G. & Nishiyama, A. The intrarenal renin-angiotensin system: from physiology to the pathobiology of hypertension and kidney disease. Pharmacol. Rev. 59, 251–287 (2007).

    Article  CAS  PubMed  Google Scholar 

  90. Rautureau, Y. & Schiffrin, E. L. Endothelin in hypertension: an update. Curr. Opin. Nephrol. Hypertens. 21, 128–136 (2012).

    Article  CAS  PubMed  Google Scholar 

  91. Clavell, A. L., Stingo, A. J., Margulies, K. B., Brandt, R. R. & Burnett, J. C. Jr. Role of endothelin receptor subtypes in the in vivo regulation of renal function. Am. J. Physiol. 268, F455–F460 (1995).

    CAS  PubMed  Google Scholar 

  92. Verhaar, M. C. et al. Endothelin-A receptor antagonist-mediated vasodilatation is attenuated by inhibition of nitric oxide synthesis and by endothelin-B receptor blockade. Circulation 97, 752–756 (1998).

    Article  CAS  PubMed  Google Scholar 

  93. Kelland, N. F. et al. Endothelial cell-specific ETB receptor knockout: autoradiographic and histological characterisation and crucial role in the clearance of endothelin-1. Can. J. Physiol. Pharmacol. 88, 644–651 (2010).

    Article  CAS  PubMed  Google Scholar 

  94. Ahn, D. et al. Collecting duct-specific knockout of endothelin-1 causes hypertension and sodium retention. J. Clin. Invest. 114, 504–511 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Ge, Y. et al. Collecting duct-specific knockout of the endothelin B receptor causes hypertension and sodium retention. Am. J. Physiol. Renal Physiol. 291, F1274–F1280 (2006).

    Article  CAS  PubMed  Google Scholar 

  96. Ge, Y., Stricklett, P. K., Hughes, A. K., Yanagisawa, M. & Kohan, D. E. Collecting duct-specific knockout of the endothelin A receptor alters renal vasopressin responsiveness, but not sodium excretion or blood pressure. Am. J. Physiol. Renal Physiol. 289, F692–F698 (2005).

    Article  CAS  PubMed  Google Scholar 

  97. Koyama, H. et al. Plasma endothelin levels in patients with uraemia. Lancet 1, 991–992 (1989).

    Article  CAS  PubMed  Google Scholar 

  98. Lehrke, I., Waldherr, R., Ritz, E. & Wagner, J. Renal endothelin-1 and endothelin receptor type B expression in glomerular diseases with proteinuria. J. Am. Soc. Nephrol. 12, 2321–2329 (2001).

    CAS  PubMed  Google Scholar 

  99. Goddard, J. et al. Endothelin A receptor antagonism and angiotensin-converting enzyme inhibition are synergistic via an endothelin B receptor-mediated and nitric oxide-dependent mechanism. J. Am. Soc. Nephrol. 15, 2601–2610 (2004).

    Article  CAS  PubMed  Google Scholar 

  100. Goddard, J. et al. Endothelin-A receptor antagonism reduces blood pressure and increases renal blood flow in hypertensive patients with chronic renal failure: a comparison of selective and combined endothelin receptor blockade. Circulation 109, 1186–1193 (2004).

    Article  CAS  PubMed  Google Scholar 

  101. Harris, R. C. et al. Cyclooxygenase-2 is associated with the macula densa of rat kidney and increases with salt restriction. J. Clin. Invest. 94, 2504–2510 (1994).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Kömhoff, M., Grone, H. J., Klein, T., Seyberth, H. W. & Nüsing, R. M. Localization of cyclooxygenase-1 and -2 in adult and fetal human kidney: implication for renal function. Am. J. Physiol. 272, F460–F468 (1997).

    PubMed  Google Scholar 

  103. Nantel, F. et al. Immunolocalization of cyclooxygenase-2 in the macula densa of human elderly. FEBS Lett. 457, 475–477 (1999).

    Article  CAS  PubMed  Google Scholar 

  104. Brater, D. C., Harris, C., Redfern, J. S. & Gertz, B. J. Renal effects of COX-2-selective inhibitors. Am. J. Nephrol. 21, 1–15 (2001).

    Article  CAS  PubMed  Google Scholar 

  105. Harding, P. et al. Cyclooxygenase-2 mediates increased renal renin content induced by low-sodium diet. Hypertension 29, 297–302 (1997).

    Article  CAS  PubMed  Google Scholar 

  106. Yang, T. et al. Regulation of cyclooxygenase expression in the kidney by dietary salt intake. Am. J. Physiol. 274, F481–F489 (1998).

    Article  CAS  PubMed  Google Scholar 

  107. Johnson, A. G., Nguyen, T. V. & Day, R. O. Do nonsteroidal anti-inflammatory drugs affect blood pressure? A meta-analysis. Ann. Intern. Med. 121, 289–300 (1994).

    Article  CAS  PubMed  Google Scholar 

  108. Pope, J. E., Anderson, J. J. & Felson, D. T. A meta-analysis of the effects of nonsteroidal anti-inflammatory drugs on blood pressure. Arch. Intern. Med. 153, 477–484 (1993).

    Article  CAS  PubMed  Google Scholar 

  109. Harris, R. C. COX-2 and the kidney. J. Cardiovasc. Pharmacol. 47 (Suppl. 1), S37–S42 (2006).

    Article  CAS  PubMed  Google Scholar 

  110. Whelton, A. Renal and related cardiovascular effects of conventional and COX-2-specific NSAIDs and non-NSAID analgesics. Am. J. Ther. 7, 63–74 (2000).

    Article  CAS  PubMed  Google Scholar 

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  1. Department of Transplantation, Mayo Clinic Florida, 4500 San Pablo Road, Jacksonville, 32224, FL, USA

    Hani M. Wadei

  2. Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic Rochester, 200 First Street SW, Rochester, 55905, MN, USA

    Stephen C. Textor

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Correspondence to Hani M. Wadei.

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Wadei, H., Textor, S. The role of the kidney in regulating arterial blood pressure. Nat Rev Nephrol 8, 602–609 (2012). https://doi.org/10.1038/nrneph.2012.191

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