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Large arteries and angiotensin II blockade in hypertension

Artery Research volume 4, pages 67–74 (2010)Cite this article

Abstract

Renin-angiotensin blockade has reduced cardiovascular morbidity and mortality in hypertensive subjects. Experimental studies have shown that this blockade acts primarily on vascular tone, causing quasi simultaneously a decrease in vascular resistance, an increase in large artery compliance and a change in endothelial function independent of blood pressure changes. In hypertensive models, the reduction of arterial hypertensive hypertrophy is proportional to blood pressure reduction while the reduction of collagen is responsible for the elasticity improvement and only dependent on angiotensin II. Molecular biology shows that, under the control of MAP-kinase, the major substratum of the action is the biochemical complex between the integrin alpha5 beta1 and its ligand fibronectin, both highly sensitive to mechanical pulsatility and effects on collagen fibers. Following the Reason study, numerous therapeutic trials in hypertension have shown not only the antihypertensive effect of this complex but also its impact on pulsatility and finally on central systolic and pulse pressure.

References

  1. Westerhof BE, Stergiopulos N, Noble MIM. Snapshots of hemodynamics. An aid for clinical research and graduate education. London: Springer; 2004. p. 97–146.

  2. Nichols WW, O’Rourke MF. McDonald’s blood flow in arteries. Theoretical, experimental and clinical principles. 4th ed. London: Edward Arnold; 2006. pp. 49–94, 193–233, 339–402, 435–502.

  3. Safar ME, Levy BI, Struijker-Boudier H. Current perspectives on arterial stiffness and pulse pressure in hypertension and cardiovascular diseases. Circulation 2003;107:2864–9.

    Google Scholar 

  4. Safar ME, O’Rourke MF. Arterial stiffness in hypertension, in handbook of hypertension. Edinburgh: Elsevier; 2006. pp. 3–62, 75–136, 459–501.

  5. Girerd X, Mourad JJ, Copie X, et al. Noninvasive detection of an increased vascular mass in untreated hypertensive patients. Am J Hypertens 1994;7:1076–84.

    Google Scholar 

  6. Roman MJ, Saba PS, Pini R, et al. Parallel cardiac and vascular adaptation in hypertension. Circulation 1992;86:1909–18.

    Google Scholar 

  7. Hayoz D, Rutschmann B, Perret F, et al. Conduit artery compliance and distensibility are not necessarily reduced in hypertension. Hypertension 1992;20:1–6.

    Google Scholar 

  8. Levy BI, Michel JB, Salzmann JL, et al. Effects of chronic inhibition of converting enzyme on mechanical and structural properties of arteries in rat renovascular hypertension. Circ Res 1988;63:227–39.

    Google Scholar 

  9. van Gorp AW, van Ingen Schenau DS, Hoeks AP, Struijker Boudier HA, Reneman RS, De Mey JG. Aortic wall properties in normotensive and hypertensive rats of various ages in vivo. Hypertension 1995;26:363–8.

    Google Scholar 

  10. Levy BI, Benessiano J, Poitevin P, Safar ME. Endothelium-dependent mechanical properties of the carotid artery in WKY and SHR. Role of angiotensin converting enzyme inhibition. Circ Res 1990;66:321–8.

    Google Scholar 

  11. Levy BI, el Fertak L, Pieddeloup C, Barouki F, Safar ME. Role of endothelium in the mechanical response of the carotid arterial wall to calcium blockade in spontaneously hypertensive and Wistar-Kyoto rats. J Hypertens 1993;11:57–63.

    Google Scholar 

  12. Benetos A, Pannier B, Brahimi M, Safar ME, Levy Bl. Doserelated changes in the mechanical properties of the carotid artery in WKY rats and SHR following relaxation of arterial smooth muscle. J Vasc Res 1993;30:23–9.

    Google Scholar 

  13. Benetos A, Elfertak L, Safar M, Levy Bl. Effects of bradykinin on carotid artery compliance: the role of the endothelium. J Hypertens Suppl 1991;9:S204–5.

    Google Scholar 

  14. Caputo L, Tedgui A, Levy Bl. Control of carotid vasomotor tone by local renin-angiotensin system in normotensive and spontaneously hypertensive rats. Role of endothelium and flow. Circ Res 1995;77:303–9.

    Google Scholar 

  15. Kato H, Suzuki H, Tajima S, et al. Angiotensin II stimulates collagen synthesis in cultured vascular smooth muscle cells. J Hypertens 1991;9:17–22.

    Google Scholar 

  16. Albaladejo P, Bouaziz H, Duriez M, et al. Angiotensin converting enzyme inhibition prevents the increase in aortic collagen in rats. Hypertension 1994;23:74–82.

    Google Scholar 

  17. Benetos A, Levy BI, Lacolley P, Taillard F, Duriez M, Safar ME. Role of angiotensin II and bradykinin on aortic collagen following converting enzyme inhibition in spontaneously hypertensive rats. Arterioscler Thromb Vasc Biol 1997;17: 3196–201.

    Google Scholar 

  18. Kool MJ, Lustermans FA, Breed JG, et al. The influence of perindopril and the diuretic combination amiloride+hydrochlorothiazide on the vessel wall properties of large arteries in hypertensive patients. J Hypertens 1995;13:839–48.

    Google Scholar 

  19. Chau NP, Simon A, Vilar J, Cabrera-Fischer E, Pithois-Merli I, Levenson J. Active and passive effects of antihypertensive drugs on large artery diameter and elasticity in human essential hypertension. J Cardiovasc Pharmacol 1992;19:78–85.

    Google Scholar 

  20. Laurent S, Caviezel B, Beck L, et al. Carotid artery distensibility and distending pressure in hypertensive humans. Hypertension 1994;23:878–83.

    Google Scholar 

  21. Kool MJ, van Merode T, Reneman RS, Hoeks AP, Struyker Boudier HA, Van Bortel LM. Evaluation of reproducibility of a vessel wall movement detector system for assessment of large artery properties. Cardiovasc Res 1994;28:610–4.

    Google Scholar 

  22. Richer C, Thuillez C, Giudicelli JF. Perindopril, converting enzyme blockade, and peripheral arterial hemodynamics in the healthy volunteer. J Cardiovasc Pharmacol 1987;9:94–102.

    Google Scholar 

  23. Bouthier JD, Safar ME, Benetos A, Simon AC, Levenson JA, Hugues CM. Haemodynamic effects of vasodilating drugs on the common carotid and brachial circulations of patients with essential hypertension. Br J Clin Pharmacol 1986;21:137–42.

    Google Scholar 

  24. Asmar RG, Pannier B, Santoni JP, Laurent S, London GM, Levy BI, et al. Reversion of cardiac hypertrophy and reduced arterial compliance after converting enzyme inhibition in essential hypertension. Circulation 1988;78:941–50.

    Google Scholar 

  25. Asmar RG, Journo HJ, Lacolley PJ, et al. Treatment for one year with perindopril: effect on cardiac mass and arterial compliance in essential hypertension. J Hypertens 1988;6(Suppl.):S33–9.

  26. Giannattasio C, Failla M, Stella ML, et al. Angiotensin-converting enzyme inhibition and radial artery compliance in patients with congestive heart failure. Hypertension 1995;26:491–6.

    Google Scholar 

  27. Bellissant E, Thuillez C, Richer C, Pussard E, Giudicelli JF. Noninvasive assessment of regional arteriolar and arterial dilating properties of lisinopril in healthy volunteers. J Cardiovasc Pharmacol 1994;24:500–8.

    Google Scholar 

  28. Webb DJ, Collier JG, Seidelin PH, Struthers AD. Regulation of regional vascular tone: the role of angiotensin conversion in human forearm resistance vessels. J Hypertens 1988;6(Suppl.): S57–9.

  29. Topouchian J, Asmar R, Sayegh F. Changes in arterial structure and function under trandolapril-verapamil combination in hypertension. Stroke 1999;30:1056–64.

    Google Scholar 

  30. Mombouli JV, Vanhoutte PM. Heterogeneity of endothelium-dependent vasodilator effects of angiotensin-converting enzyme inhibitors: role of bradykinin generation during ACE inhibition. J Cardiovasc Pharmacol 1992;20(Suppl. 9):S74–82.

  31. Stefas L, Levy Bl. Effects of saralasin on arterial compliance in normotensive and hypertensive rats. Role of endothelium. Hypertension 1991;18:II30–6.

    Google Scholar 

  32. Mombouli JV, Illiano S, Nagao T, Scott-Burden T, Vanhoutte PM. Potentiation of endothelium-dependent relaxations to bradykinin by angiotensin I converting enzyme inhibitors in canine coronary artery involves both endothelium-derived relaxing and hyperpolarizing factors. Circ Res 1992;71:137–44.

    Google Scholar 

  33. Hintze TH, Vatner SF. Reactive dilation of large coronary arteries in conscious dogs. Circ Res 1984;54:50–7.

    Google Scholar 

  34. Jaffe MD. High-flow dilatation. Lancet 1981;1:1237–9.

    Google Scholar 

  35. Pohl U, Holtz J, Busse R, Bassenge E. Crucial role of endothelium in the vasodilator response to increased flow in vivo. Hypertension 1986;8:37–44.

    Google Scholar 

  36. Hilton SM. A peripheral arterial conducting mechanism underlying dilatation of the femoral artery and concerned in functional vasodilatation in skeletal muscle. J Physiol 1959; 149: 93–111.

    Google Scholar 

  37. Barenbrock M, Spieker C, Hoeks AP, Zidek W, Rahn KH. Effect of lisinopril and metoprolol on arterial distensibility. Hypertension 1994;23:I161–3.

    Google Scholar 

  38. Levy BI, Michel JB, Salzmann JL, et al. Long-term effects of angiotensin-converting enzyme inhibition on the arterial wall of adult spontaneously hypertensive rats. Am J Cardiol 1993; 71:8E–16E.

  39. Chen CH, Ting CT, Lin SJ, et al. Different effects of fosinopril and atenolol on wave reflections in hypertensive patients. Hypertension 1995;25:1034–41.

    Google Scholar 

  40. Savolainen A, Keto P, Poutanen VP, et al. Effects of angiotensin-converting enzyme inhibition versus beta-adrenergic blockade on aortic stiffness in essential hypertension. J Cardiovasc Pharmacol 1996;27:99–104.

    Google Scholar 

  41. Girerd X, Giannattasio C, Moulin C, Safar M, Mancia G, Laurent S. Regression of radial artery wall hypertrophy and improvement of carotid artery compliance after long-term antihypertensive treatment in elderly patients. J Am Coll Cardiol 1998;31:1064–73.

    Google Scholar 

  42. London GM, Pannier B, Guerin AP, Marchais SJ, Safar ME, Cuche JL. Cardiac hypertrophy, aortic compliance, peripheral resistance, and wave reflection in end-stage renal disease. Comparative effects of ACE inhibition and calcium channel blockade. Circulation 1994;90:2786–96.

    Google Scholar 

  43. Ting CT, Yang TM, Chen JW, Chang MS, Yin FC. Arterial hemodynamics in human hypertension. Effects of angiotensin converting enzyme inhibition. Hypertension 1993;22:839–46.

    Google Scholar 

  44. London GM, Asmar RG, O’Rourke MF, Safar MEon behalf of the REASON project. Mechanism(s) of selective systolic blood pressure reduction after a low-dose combination of perindopril/indapamide in hypertensive subjects: comparison with atenolol. J Am Coll Cardiol 2004;43:92–9.

    Google Scholar 

  45. de Luca N, Asmar RG, London GM, O’Rourke MF, Safar ME. Selective reduction of cardiac mass and central blood pressure on low-dose combination perindopril/indapamide in hypertensive subjects. J Hypertens 2004;22:1623–30.

    Google Scholar 

  46. Protogerou A, Blacher J, Stergiou GS, Achimastos A, Safar ME. Blood pressure response under chronic antihypertensive drug therapy: the role of aortic stiffness in the REASON (Preterax in Regression of Arterial Stiffness in a Controlled Double-Blind) study. J Am Coll Cardiol 2009;53:445–51.

    Google Scholar 

  47. Moiseeva EP. Adhesion receptors of vascular smooth muscle cells and their functions. Cardiovasc Res 2001;52:372–86.

    Google Scholar 

  48. Ingber D. Integrins as mechanochemical transducers. Curr Opin Cell Biol 1991;3:841–8.

    Google Scholar 

  49. Wilson E, Sudhir K, Ives HE. Mechanical strain of rat vascular smooth muscle cells is sensed by specific extracellular matrix/integrin interactions. J Clin Invest 1995;96:2364–72.

    Google Scholar 

  50. Intengan HD, Schiffrin EL. Structure and mechanical properties of resistance arteries in hypertension: role of adhesion molecules and extracellular matrix determinants. Hypertension 2000;36:312–8.

    Google Scholar 

  51. Koffi I, Lacolley P, Kirchengaast M, Pomies JP, Laurent S, Benetos A. Prevention of arterial structural alterations with verapamil and trandolapril and consequences for mechanical properties in spontaneously hypertensive rats. Eur J Pharmacol 1998;361:51–60.

    Google Scholar 

  52. Labat C, Lacolley P, Lajemi M, de Gasparo M, Safar ME, Benetos A. Effects of valsartan on mechanical properties of the carotid artery in spontaneously hypertensive rats under high-salt diet. Hypertension 2001;38:439–43.

    Google Scholar 

  53. Lacolley P, Labat C, Pujol A, Delcayre C, Benetos A, Safar M. Increased carotid wall elastic modulus and fibronectin in aldosterone-salt-treated rats: effects of eplerenone. Circulation 2002;106:2848–53.

    Google Scholar 

  54. Louis H, Kakou A, Regnault V, et al. Role of alpha1beta1-integrin in arterial stiffness and angiotensin-induced arterial wall hypertrophy in mice. Am J Physiol Heart Circ Physiol 2007; 293:H2597–604.

  55. Sartore S, Scatena M, Chiavegato A, Faggin E, Giuriato L, Pauletto P. Myosin isoform expression in smooth muscle cells during physiological and pathological vascular remodeling. J Vasc Res 1994;31:61–81.

    Google Scholar 

  56. Lehoux S, Tedgui A. Cellular mechanics and gene expression in blood vessels. J Biomech 2003;36:631–43.

    Google Scholar 

  57. Fesler P, Safar ME, du Cailar G, Ribstein J, Mimran A. Pulse pressure is an independent determinant of renal function decline during treatment of essential hypertension. J Hypertens 2007;25:1915–20.

    Google Scholar 

  58. Matrougui K, Schiavi P, Guez D, Henrion D. High sodium intake decreases pressure-induced (myogenic) tone and flow-induced dilation in resistance arteries from hypertensive rats. Hypertension 1998;32:176–9.

    Google Scholar 

  59. Verhave JC, Fesler P, du Cailar G, Ribstein J, Safar ME, Mimran A. Elevated pulse pressure is associated with low renal function in elderly patients with isolated systolic hypertension. Hypertension 2005;45:586–91.

    Google Scholar 

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Authors and Affiliations

  1. Faculty of Medicine, Hôtel-Dieu Hospital, AP-HP, Diagnostics Center, Paris-Descartes University, 1 place du Parvis Notre-Dame, 75181, Paris Cedex 04, France

    Michel E. Safar

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Correspondence to Michel E. Safar.

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Safar, M.E. Large arteries and angiotensin II blockade in hypertension. Artery Res 4, 67–74 (2010). https://doi.org/10.1016/j.artres.2010.07.001

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Artery Research

ISSN: 1876-4401

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