Skip to main content

Pathogenesis of Hypertension: Vascular Mechanisms

  • Chapter
Atlas of Hypertension

Abstract

The mechanisms involved in the pathogenesis of hypertension are increasingly well understood. The focus classically has been on neural and humoral stimuli of vascular constriction and on endocrine and renal stimuli that control blood volume. It has become clear that strong environmental and genetic influences converge to result in the hypertensive phenotype [1]. With the development of the science of vascular biology in recent years there has been increasing focus on the blood vessel wall itself in the pathogenesis of hypertension. The current view is that the resistance arteriole may be involved in the pathogenesis of the disease, both primarily and secondarily. Hemodynamic, neural, and humoral factors or mechanisms intrinsic to the vessel wall itself may initiate contractile or structural changes that result in initial increases in pressure. The adaptive changes in the arteriole in response to an elevated intravascular pressure perpetuate and probably worsen the hypertension. Significant new insights have been developed into both functional and structural changes that may contribute to the initiation and/or progression of this condition.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 74.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Berk BC, Alexander RW: Biology of the vascular wall in hypertension. In The Kidney. Edited by Brenner BM. Philadelphia: WB Saunders; 1995:2049–2070.

    Google Scholar 

  2. Reilly DF, Gordon D, Schwartz SM: Determination and comparison of the aortic polyploid smooth muscle content of human hypertensive subjects and normotensive controls. Acta Physiol Scand 1988,571:181–188.

    CAS  Google Scholar 

  3. Folkow B, Hallback M, Lundgren Y, et al.: Background of increased flow resistance and vascular reactivity in spontaneously hypertensive rats. Acta Physiol Scand 1970, 80:93–106.

    Article  PubMed  CAS  Google Scholar 

  4. Lüscher TF, Vanhoutte PM: Endothelium-dependent contraction to acetylcholine in the aorta of the spontaneously hypertensive rat. Hypertension 1986, 8:344–348.

    Article  PubMed  Google Scholar 

  5. Moncada S, Palmer RM, Higgs EA: Nitric oxide: physiology, pathophysiology and pharmacology. Pharmacol Rev 1991,43:109–142.

    PubMed  CAS  Google Scholar 

  6. Hüttner I, Gabbiani G: Vascular endothelium in hypertension. In Hypertension. Edited by Genest J, Kuchel O, Hamet P, Cantin M. New York: McGraw-Hill; 1983.

    Google Scholar 

  7. Treasure CB, Klein JL, Vita JA, et al.: Hypertension and left ventricular hypertrophy are associated with impaired endothelium-mediated relaxation in human coronary resistance vessels. Circulation 1993, 87:86–93.

    Article  PubMed  CAS  Google Scholar 

  8. Harrison DG: Endothelial function and oxidant stress [review]. Clin Cardiol 1997,20 (11 Suppl 2):II-ll-7.

    Google Scholar 

  9. Hagashi Y, Sasaki S, Nakagawa K, et al.: Endothelial function and oxidative stress in renovascular hypertension. N Engl J Med 2002, 346:1954–1962.

    Article  Google Scholar 

  10. Linder L, Kiowski W, Buhler FR, et al.: Indirect evidence for release of endothelium-derived relaxing factor in human forearm circulation in vivo: blunted response in essential hypertension. Circulation 1990, 81:1762–1767.

    Article  PubMed  CAS  Google Scholar 

  11. Owens GK, Schwartz SM: Vascular smooth muscle cell hypertrophy and hyperploidy in the Goldblatt hypertensive rat. Circ Res 1983,53:491–501.

    Article  PubMed  CAS  Google Scholar 

  12. Halpern W, Warshaw DM, Mulvany MJ: Mechanical and morphological properties of arterial resistance vessels in young and old spontaneously hypertensive rats.Circ Res 1979,45:250–259.

    Article  PubMed  Google Scholar 

  13. Harper RN, Moore MA, Marr MC, et al: Arteriolar rarefaction in the conjunctiva of human essential hypertensives. Microvasc Res 1978,16:369–372.

    Article  PubMed  CAS  Google Scholar 

  14. Fagrell B, Gundersen J: Capillary blood flow in the nail fold in relation to the digital systolic blood pressure. Vasa 1975,4:250–257.

    PubMed  CAS  Google Scholar 

  15. Wolf S, Arend O, Schulte K, et al: Quantification of retinal capillary density and flow velocity in patients with essential hypertension. Hypertension 1994,23:464–467.

    Article  PubMed  CAS  Google Scholar 

  16. Doyle AE, Fraser JRE: Vascular reactivity in hypertension.Circ Res 1961, 9:755–761.

    Article  PubMed  CAS  Google Scholar 

  17. Ushio-Fukai M, Zafari AM, Fukui T, et al: p22phox is a critical component of the superoxide-generating NADH/NADPH oxidase system and regulates angiotensin II-induced hypertrophy in vascular smooth muscle cells. J Biol Chem 1996,271:23317–23321.

    Article  PubMed  CAS  Google Scholar 

  18. Rajagopalan S, Kurz S, Mùnzel T, et al: Angiotensin II mediated hypertension in the rat increases vascular superoxide production via membrane NADH/NADPH oxidase activation: contribution to alterations of vasomotor tone. J Clin Invest 1996, 97:1916–1923.

    Article  PubMed  CAS  Google Scholar 

  19. Bech-Laursen J, Rajagopalan S, Tarpey M, et al: A role of superoxide in angiotensin II-but not catecholamine-induced hypertension. Circulation 1997, 95:588–593.

    Article  Google Scholar 

  20. Nakazono K, Watanabe N, Matsuno K, et al: Does superoxide underlie the pathogenesis of hypertension? Proc Natl Acad Sci USA 1991, 88:10045–10048.

    Article  PubMed  CAS  Google Scholar 

  21. Fukui T, Ishizaka N, Rajagopalan S, et al: p22phox mRNA expression and NADPH oxidase activity are increased in aortas from hypertensive rats. Circ Res 1997, 80:45–51.

    Article  PubMed  CAS  Google Scholar 

  22. Russo C, Olivieri O, Girelli D, et al: Anti-oxidant status and lipid peroxidation in patients with essential hypertension. J Hypertens 1998,16:1267–1271.

    Article  PubMed  CAS  Google Scholar 

  23. Landmesser U, Cai H, Dikalov S, et al: Role of p47P hox in vascular oxidative stress and caused by angiotensin II. Hypertension 2002, 40:511–515.

    Article  PubMed  CAS  Google Scholar 

  24. Somers MJ, Mavromatis K, Galis ZS, Harrison DG: Vascular superoxide production and vasomotor function in hypertension induced by deoxycorticosterone acetate-salt. Circulation 2000, 101 (14):1722–1728.

    Article  PubMed  CAS  Google Scholar 

  25. Laursen JB, Somers M, Kurz S, et al: Endothelial regulation of vasomotion in apoE-deficient mice: implications for interactions between peroxynitrite and tetrahydrobiopterin. Circulation 2001, 103(9):1282–1288.

    Article  PubMed  CAS  Google Scholar 

  26. Hong HJ, Hsiao G, Cheng TH, Yen MH: Supplemention with tetrahydrobiopterin suppresses the development of hypertension in spontaneously hypertensive rats. Hypertension 2001, 38 (5):1044–1048.

    Article  PubMed  CAS  Google Scholar 

  27. Fukai T, Siegfried MR, Ushio-Fukai M, et al: Modulation of extracellular superoxide dismutase expression by angiotensin II and hypertension. Circ Res 1999, 85:23–28.

    Article  PubMed  CAS  Google Scholar 

  28. Imig JD, Falck JR, Wei S, et al: Epoxygenäse metabolites contribute to nitric oxide-independent afferent arteriolar vasodilation in response to bradykinin. J Vase Res 2001,38:247–255.

    Article  CAS  Google Scholar 

  29. Fleming I: Cytochrome p450 and vascular homeostasis. Circ Res 2001, 89:753–762.

    Article  PubMed  CAS  Google Scholar 

  30. Fisslthaler B, Popp R, Kiss L, et al: Cytochrome P450 2C is an EDHF synthase in coronary arteries. Nature 1999,401:493–497.

    Article  PubMed  CAS  Google Scholar 

  31. Griendling KK, Alexander RW: Cellular biology of blood vessels. In Hurst’s The Heart. Edited by Schlant RC, Alexander RW, O’Rourke R, et al. New York: McGraw-Hill; 1994:31–15.

    Google Scholar 

  32. Harrison D: The endothelial cell. Heart Dis Stroke 1992,1:95–99.

    PubMed  CAS  Google Scholar 

  33. Deal JE, Shah V, Goodenough V, et al: Red cell membrane sodium transport: possible genetic role and use in identifying patients at risk of essential hypertension. Arch Dis Child 1990, 65:1154–1157.

    Article  PubMed  CAS  Google Scholar 

  34. Aviv A, Lasker N: Proposed defects in membrane transport and intracellular ions as pathogenetic factors in essential hypertension. In Hypertension: Pathophysiology, Diagnosis, and Management. Edited by Laragh JH, Brenner BM: New York: Raven Press; 1990:923–937.

    Google Scholar 

  35. Taddei S, Ghiadoni L, Virdis A, et al: Vasodilation to bradykinin is mediated by an ouabain-sensitive pathway as a compensatory mechanism for impaired nitric oxide availability in essential hypertensive patients. Circulation 1999,100:1400–1405.

    Article  PubMed  CAS  Google Scholar 

  36. Dudley CRK, Taylor DJ, Ng LL, et al: Evidence for abnormal Na+/H+ antiport activity detected by phosphorus nuclear magnetic resonance spectroscopy in exercising skeletal muscle of patients with essential hypertension. Clin Sci 1990, 79:791–797.

    Google Scholar 

  37. Rosskopf D, Fromter E, Siffert W: Hypertensive sodium-proton exchanger phenotype persists in immortalized lymphoblasts from essential hypertensive patients.J Clin Invest 1993,92:2553–2559.

    Article  PubMed  CAS  Google Scholar 

  38. Lifton RP, Hunt SC, Williams RR, et al: Exclusion of the Na+/H+ antiporter as a candidate gene in human essential hypertension. Hypertension 1991,17:8–14.

    Article  PubMed  CAS  Google Scholar 

  39. Rosskopf D, Dusing R, Siffert W: Membrane sodium-proton exchange and primary hypertension. Hypertension 1993,21:607–617.

    Article  PubMed  CAS  Google Scholar 

  40. Berk BC, Vallega G, Muslin AJ, et al: Spontaneously hypertensive rat vascular smooth muscle cells in culture exhibit increased growth and Na+/H+ exchange. J Clin Invest 1989,83:822–829.

    Article  PubMed  CAS  Google Scholar 

  41. Rebbeck TR, Turner ST, Michels V, et al: Genetic and environmental explanations for the distribution of sodium-lithium countertransport in pedigrees from Rochester, MN.Am J Hum Genet 1991,48:1092–1104.

    PubMed  CAS  Google Scholar 

  42. Turner ST, Rebbeck TR, Sing CF: Sodium-lithium countertransport and probability of hypertension in Caucasians 47 to 89 years old. Hypertension 1992,20:841–850.

    Article  PubMed  CAS  Google Scholar 

  43. Resink TJ, Tkachuk VA, Erne P, et al: Platelet membrane Ca2+-ATPase: blunted calmodulin-stimulation in essential hypertension. J Hypertens 1985,3:S37–S40.

    CAS  Google Scholar 

Download references

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2003 Springer Science+Business Media New York

About this chapter

Cite this chapter

Alexander, R.W., Hennigar, R.A., Griendling, K.K. (2003). Pathogenesis of Hypertension: Vascular Mechanisms. In: Hollenberg, N.K. (eds) Atlas of Hypertension. Current Medicine Group, London. https://doi.org/10.1007/978-1-4615-6493-5_4

Download citation

  • DOI: https://doi.org/10.1007/978-1-4615-6493-5_4

  • Publisher Name: Current Medicine Group, London

  • Print ISBN: 978-1-4615-6495-9

  • Online ISBN: 978-1-4615-6493-5

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics