Drugs 46 (Suppl. 2): 82-87, 1993 0012-6667/93/0200-0082/$3.00/0 © Adis International Limited. All rights reserved.

DRSUP3617

Arterial Compliance and Blood Pressure s.J. Marchais, A.P. Guerin, B. Pannier, G. Delavaud and G.M. London Department of Nephrology, Manhes Hospital, FJeury-Merogis, France

Summary As a result of the dual function of arteries, the conduit and cushioning functions, arterial pressure has 2 components: the steady component, characterised by mean blood pressure, and the pulsatile component, characterised by pulse pressure. Arterial compliance mostly depends on arterial intrinsic elastic properties, and is a determinant of the propagation speed of the pulse pressure wave. Decreased arterial compliance is responsible for both an increase in the incident pressure wave and the higher effect of reflected pressure waves. This increases systolic pressure and ventricular afterload, and generates left ventricular hypertrophy.

Arterial structural changes that accompany the aging process result in a loss of distensibility and compliance. In essential as well as in secondary hypertension, arterial compliance is reduced, and age-related structural changes of the arterial wall are accelerated. Whet/ler the change in arterial compliance is a passive consequence of the increase in blood pressure or is related to changes in the arterial wall structure remains unclear.

Calcium antagonists improve the distensibility and compliance of large and small arteries, contributing significantly to the improvement in the management of essential and secondary hypertension.

Epidemiological studies have emphasised the close relationship between blood pressure and the incidence of cardiovascular diseases (Kannel & Stokes 1985; Tverdal 1987). Clinical hypertension is usually classified on the basis of raised diastolic blood pressure, which is attributed to vasoconstric­tion of small arteries and the resultant increase in vascular resistance. However, during recent years, systolic blood pressure and pulse pressure have been recognised to be of major importance in determin­ing cardiovascular morbidity and mortality (Curb et al. 1985; Dame et al. 1989; Dyer et al. 1985; Kannel et al. 1971; Rutan et al. 1988). It has been shown that large conduit arteries, in addition to the small arteries, play an important role in determin­ing the shape and amplitude of the blood pressure wave, directly influencing the level of systolic, dia­stolic and pulse pressures (O'Rourke 1982). In this

paper, we briefly analyse the role of arterial com­pliance in arterial hypertension.

1. Functions of the Arterial System

The arterial system has 2 distinct, but inter­related functions: a conduit function, i.e. delivering an adequate supply of blood to body tissues, and a cushioning function, i.e. ~moothing out pressure pulses occurring as a result of intermittent ven­tricular ejection (Nichols &. O'Rourke 1991).

1.1 Conduit Function of Arteries

In their role as conduits, arteries must deliver an adequate supply of blood from the heart to peri­pheral organs and tissues. For efficient metabolic exchange, a continuous, steady blood flow is re-

Arterial Compliance and Blood Pressure

quired. To maintain this blo<?d flow, the mean ar­terial pressure must be steady and high enough to overcome any resistance to flow. Therefore, the function of arteries as conduits is related exclu­sively to steady (mean) blood pressure and blood flow, and the relationship between them. This re­lationship defines vascular resistance (Nichols & O'Rourke 1991; O'Rourke 1982; O'Rourke & A vo­lio 1980). The mean blood pressure is determined entirely by cardiac output and vascular resistance. The efficiency of arteries in their role as conduits depends on both the calibre of the arteries and the uniformity of mean blood pressure. Abnormal con­duit function results from narrowing or obstruc­tion of the arterial lumen, and may result in is­chaemia or infarction in the organ and tissues downstream from the region of arterial pathology (O'Rourke 1982).

1.2 Cushioning Function of Arteries

Arteries also act as cushions to reduce the pres­sure oscillations resulting from intermittent ven­tricular ejection. The cushioning function of arter­ies is characterised by pulsatile flow and pulsatile pressure (pulse pressure) [Nichols & O'Rourke 1991; O'Rourke 1982; O'Rourke & Avolio 1980]. Large arteries can instantaneously accommodate blood ejected from the heart. They store part of the stroke volume during systolic ejection, draining this volume into smaller arteries during diastole. Thus, continuous perfusion of organs and tissues is en­sured. This dampening ('Windkessel') effect is re­lated to the viscoelastic properties of arterial walls, i.e arterial compliance and distensibility. The ca­pability of the aorta and large arteries to instan­taneously accommodate the volume ejected by the left ventricle depends on their compliance. The ef­ficiency of the cushioning function is altered prin­cipally by decreased arterial compliance, or by stiffening of the arterial wall (Avolio et al. 1983; Nichols & O'Rourke 1991; O'Rourke 1982; O'Rourke & Avolio 1980).

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2. Arterial Compliance

Compliance is a term describing the amount of change in vessel wall dimension after application of stress. In physiology, compliance is defined as the change in volume (dV) resulting from a change in pressure (dP), i.e. compliance (C) = dV/dP. The reciprocal value of compliance is the elastance (E) [E = dP/dVl Compliance represents the slope of the pressure-volume relationship (or for arteries the slope of the pressure-diameter relationship; see fig. 1) at any point on the pressure-volume curve. The structural composition of the arterial media deter­mines the compliance of the artery (O'Rourke 1982). As the arterial media is composed of both smooth muscle cells and connective tissue (con­taining elastin and collagen fibres), the pressure­diameter relationship is nonlinear (fig. 1) [Nichols & O'Rourke 1991; O'Rourke 1982; O'Rourke & Avolio 1980]. When the distending pressure is low, the tension is borne by elastin fibres and compli­ance is high; when the distending pressure is high, the tension is borne predominantly by the less ex­tendible collagen fibres and the arterial wall is less compliant. Thus, compliance can be defined only in terms of a given pressure. Compliance depends partly on blood pressure, but more importantly on the intrinsic elastic properties and composition of the arterial wall.

2.1 Effects of Arterial Compliance on Systolic, Diastolic and Mean Blood Pressure

As a consequence of the dual function of arter­ies, it appears that arterial pressure has 2 compo­nents: 1) a steady component (mean blood pres­sure); and 2) a pulsatile component (pulse pressure), which represents oscillation around mean blood pressure, with systolic and diastolic pressures being the highest and lowest points of this oscillation (O'Rourke 1982). The respective magnitudes of the 2 components of blood pressure are determined by characteristics of the arterial system (small and large arteries included) in accepting pulsatile flow from the heart, i.e. aortic input impedance.

Aortic input impedance, which is determined

84 Drugs 46 (Suppl. 2) 1993

... ~ E <11 is

Pressure i :::> Fig. 1. The arterial pressure-diameter relationship; the slope (-0-) at any given pressure defines arterial compliance. Drugs may increase compliance passively through pressure-dependent changes (e.g. compliance moves from A to B), or actively by changing the pressure-diameter curve (e.g. compliance moves from A to D or from A to C).

by arteriolar tone and peripheral resistance, aortic compliance and distensibility, and the amplitude and timing of arterial wave reflections, defines left ventricular afterload. Thus, as a determinant of aortic impedance and ventricular afterload, arterial compliance has an important role in the patho­physiology of hypertension.

A decrease in arterial compliance has detrimen­tal upstream effects on the heart. Reduced arterial compliance causes increased systolic pressure, and a relative decrease in aortic diastolic pressure, with an inadequate increase in pulse pressure (Nichols & O'Rourke 1991; O'Rourke 1982; O'Rourke & Avolio 1980). The magnitude of the pulse pressure is determined by the interaction of an incident pressure wave generated by left ventricular ejec­tion, and reflected wave(s) generated by the arterial system. Alterations in arterial compliance influ­ence both incident and reflected waves. The mag­nitude of the incident pressure wave depends on

the pattern of left ventricular ejection and on ar­terial compliance, the amplitude of the incident pressure wave being increased when arterial com­pliance is low. The effect of reflected waves on pulse pressure and systolic pressure depends on the in­tensity of reflection, the propagation properties of the arterial tree and the timing of incident and re­flected waves. As arterial compliance is a deter­minant of the propagation speed of the pulse pres­sure wave, it influences the timing of incident and reflected waves. When arterial compliance is de­creased, pressure waves are propagated along the arteries more rapidly, returning to the heart from reflective sites before ventricular ejection has ceased (Kelly et al. 1989; London et al. 1990; Nichols & O'Rourke 1991; O'Rourke 1982; O'Rourke & A vo­lio 1980). This early return of wave reflections in­duces an increase in peak systolic pressure, mean systolic pressure and end-systolic pressure, and a decrease in pressure during diastole. Thus, de-

Arterial Compliance and Blood Pressure

creased arterial compliance produces both an in­crease in the incident pressure wave and an in­creased effect of reflected pressure waves (Kelly et al. 1989; London et al. 1990; Nichols & O'Rourke 1991; O'Rourke 1982; O'Rourke & Avolio 1980). The subsequent rise in systolic pressure increases myocardial oxygen consumption, while the reduc­tion in diastolic pressure tends to reduce coronary blood flow. The increase in systolic pressure also increases ventricular afterload, altering ventricular ejection and resulting in left ventricular hypertro­phy.

2.2 Changes in Arterial Compliance

2.2.1 Changes Resulting from Aging With aging, the arterial wall thickens and the

arteries dilate and lengthen and become less com­pliant (Avolio et al. 1983; Fleckenstein 1984; Mitchell & Schwartz 1965; Nichols & O'Rourke 1991; O'Rourke 1982; Wolinsky 1972). The major changes occur in the media and intima, affecting the elastic fibres and laminae that are principally responsible for vessel distensibility. The orderly ar­rangement of elastic laminae is lost, and ,is replaced by thinning, splitting and fragmentation. This de­generation of elastic fibres is associated with an in­crease in collagen fibres and ground substance, and in calcium deposition (O'Rourke 1982; O'Rourke et al. 1987). Calcinosis appears to be an inevitable consequence of aging, even in the absence of ath­eroma or occlusive lesions (Fleckenstein 1984; Fleckenstein et al. 1983). The principal functional alteration in the arterial wall that occurs with aging is arterial stiffening because ofloss of distensibility and compliance. As a result, the aortic pulse wave velocity increases with aging. This has 2 important consequences: 1) an increase in the incident pres­sure wave; and 2) an early return of wave reflec­tions, resulting in elevated peak and end-systolic pressures and ventricular/vascular mismatch.

2.2.2 Changes Resulting from Hypertension Several studies in man have shown that the

cushioning function of arteries is altered in essen­tial and secondary hypertension (Arcaro et al. 1990;

85

Guerin et al. 1992; Hugue et al. 1988; Isnard et al. 1989; Laurent et al. 1988; Nichols & O'Rourke 1991; Safar et al. 1983), and age-related changes in the arterial wall are accelerated. Arterial compli­ance is reduced in systemic and brachial circula­tions in isolated systolic hypertension in elderly patients, in patients with hypertension related to end-stage renal disease, in middle-aged patients with sustained systolic-diastolic hypertension, and even in young subjects with borderline hypertension (O'Rourke 1982; Safar & Simon 1986; Safar et al. 1987). It is unclear whether changes in arterial compliance are a passive consequence of hyper ten­sion or are related to a change in arterial wall struc­ture. As with the aging process, hypertension de­creases arterial compliance and increases pulse wave velocity, resulting in an early return of wave re­flections and, thus, contributing to a loss of left ventricular function.

3. The Effect of Antihypertensive Treatment

Arterial compliance is a determinant of the in­cident pressure wave, pulse wave velocity, and the timing of incident and reflected waves. Therefore, arterial compliance influences blood pressure di­rectly. Almost all antihypertensive regimens could increase compliance in the long term as a conse­quence of the drug-induced reduction in mean blood pressure (fig. 1). A reduction in mean blood pressure per se will increase arterial distensibility and reduce pulse wave velocity, thus delaying wave reflections. {1-Blocking drugs also increase the amount of reflected pressure (reflection coefficient) and, by increasing the duration of ejection, may favour the summation of incident and reflected waves in the central arteries and the aorta (Guerin et al. 1992). In contrast, drugs such as angiotensin converting enzyme (ACE) inhibitors and calcium antagonists, which have a direct (blood pressure independent) vasorelaxing effect on large and small arteries, can reduce blood pressure not only by in­creasing compliance but also by decreasing wave reflections (Guerin et al. 1992; Kelly et al. 1989).

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3.1 Calcium Antagonists

Short and long term administration of dihydro­pyridine derivatives to patients with essential or secondary hypertension caused a significant in­crease in arterial compliance in the systemic and brachial circulations (Curb et al. 1985; Levenson et al. 1983, 1984, 1985). There are several possible mechanisms that may account for the increased ar­terial compliance caused by calcium antagonists (Milnor 1982; O'Rourke 1982; Safar & London 1987). Firstly, blood pressure reduction per se may favour an increase in compliance, since the stretch of the arterial wall is lower when blood pressure is reduced (fig. I). Secondly, drug effects on arterial smooth muscle may result in relaxation of the ar­terial wall. Finally, a long term reduction in blood pressure may induce remodelling of arterial walls, decreasing arterial hypertrophy and modifying the content of elastin vs collagen. The ability of cal­cium antagonists to cause vasodilation in the large and small arteries may account for the superiority of calcium antagonists compared with pure arter­iolar vasodilators in increasing arterial compliance. Indeed, calcium antagonists have been shown to increase compliance, decrease wave reflections, and delay the return of reflected waves. Improvement in the compliance of peripheral conduit arteries was shown after administration of dihydropyridines and diltiazem (Levenson et al. 1983, 1984, 1985). Sim­ilarly, arterial vasorelaxation and improved disten­sibility were observed in carotid arteries after administration of verapamil (Van Merode et al. 1990) and in the aorta after administration of ni­trendipine (Guerin et al. 1992). Increased arterial compliance and a reduction in wave reflections with calcium antagonist therapy may account for the su­perior effect of these drugs, compared with pure vasodilators, on the regression of left ventricular hypertrophy (Schulman et al. 1990).

4. Conclusions

Arterial compliance is one of the principal de­terminants of aortic input impedance and left ven­tricular afterload. Since it directly influences the

Drugs 46 (Suppl. 2) 1993

amplitude of the incident pressure wave and the timing of wave reflections, arterial compliance is an important determinant of pulse pressure and systolic blood pressure. Reduced arterial compli­ance increases ventricular afterload, increasing oxygen consumption and leading to the develop­ment of left ventricular hypertrophy. Calcium ant­agonists improve the distensibility and compliance of large and small arteries, contributing signifi­cantly to the management of essential and second­ary hypertension.

References

Arcaro G, Laurent S, Hoeks AP, et a!. Vessel wall properties of the carotid artery in normotensive and hypertensives. Ab­stract. Circulation 80 (Supp!. 2): 594, 1990

Avolio AO, Chen SG, Wang RP, et a!. Effects of aging on chang­ing arterial compliance and left ventricular load in a Northern Chinese Urban Community. Circulation 68: 50-58, 1983

Curb JD, Borhani NO, Entwisle G, et al. Isolated systolic hyper­tension in 14 communities. American Journal of Epidemiology 121: 362-370, 1985

Darne B, Girerd X, Safar M, et al. Pulsatile versus steady com­ponent of blood pressure: a cross-sectional and a prospective analysis on cardiovascular mortality. Hypertension 13: 392-400, 1989

Dyer AR, Stamler J, Shekelle RB, et a!. Pulse pressure. III. Prog­nostic significance in four Chicago epidemiologic studies. Jour­nal of Chronic Disease 35: 283-294, 1985

Fleckenstein A. Calcium antagonism: history and prospect for a multifaceted pharmacodynamic principle. In Opie LH (Ed.) Calcium antagonists and cardiovascular disease, pp. 9-28, Raven Press, New York, 1984

Fleckenstein A, Frey M, Fleckenstein-Grun G. Protection by cal­cium antagonists against experimental arterial calcinosis. In Pyrl K, et al. (Eds) Secondary prevention of coronary heart disease, pp. 109-122, Georg Thieme Veriag, Stuttgart, 1983

Guerin AP, Pannier BM, Marchais SJ, et al. Effects of antihyper­tensive agents on carotid pulse contour in man. Journal of Human Hypertension 6 (Suppl. 2): S37-S40, 1992

Hugue CJ, Safar ME, Aleferakis MC, et a!. The ratio between ankle and brachial systolic pressure in patients with sustained uncomplicated essential hypertension. Clinical Sciences 74: 179-182, 1988

Isnard RN, Pannier BM, Laurent S, et al. Pulsatile diameter and elastic modulus of the aortic arch in essential hypertension: a noninvasive study. Journal of the American College of Car­diology 13: 399-406, 1989

Kannel WB, Stokes J. Hypertension as a cardiovascular risk fac­tor. In Robertson JIS (Ed.) Handbook of hypertension epi­demiology of hypertension, Vol. 6, pp. 15-34, Elsevier Science Publishing Co. Inc., New York, 1985

Kannel WB, Gordon T, Schwartz MJ. Systolic versus diastolic blood pressure and risk of coronary heart disease: the Fra­mingham Study. American Journal of Cardiology 27: 335-346, 1971

Kelly R, Daley J, Avolio A, O'Rourke M. Arterial dilation and reduced wave reflection: benefit of dilevalol in hypertension. Hypertension 14: 14-21, 1989

Laurent S, Lacolley P, London G, et al. Hemodynamics of the

Arterial Compliance and Blood Pressure

carotid artery after vasodilation in essential hypertension. Hypertension 11: 134-140, 1988

Levenson J, Simon A, Bouthier J, et al. The effect of acute and chronic nicardipine therapy on forearm arterial hemody­namics in essential hypertension. British Journal of Clinical Pharmacology 20 (Suppl. I): 107-113, 1985

Levenson JA, Simon AC, Safar ME, et al. Large arteries in hyper­tension: acute effect of a new calcium entry blocker, nitren­dipine. Journal of Cardiovascular Pharmacology 6 (Suppl. 7): 1006-1010, 1984

Levenson JA, Safar ME, Simon AC, et al. Systemic and arterial hemodynamic effect ofnifedipine (20 mg) in mild-to-moderate hypertension. Hypertension 5 (Suppl. 5): 57-60, 1983

London GM, Marchais SJ, Guerin AP, et al. Salt and water re­tention and calcium blockade in ureqIia. Circulation 82: 105-113, 1990

Milnor WR. Hemodynamics, pp. 56-96, Williams & Wilkins, Bal­timore, 1982

Mitchell JRA, Schwartz CJ. Arterial disease, pp. 87-102, Bram­well, Oxford, 1965

Nichols WW, O'Rourke MF. Vascular Impedance. In Mc­Donald's blood flow in arteries: theoretic, experimental and clinical principles, 3rd ed., pp. 283-329, Edward Arnold, Lon­don, 1991

O'Rourke MF. Vascular impedance: the relationship between pressure and flow. In Arterial function in health and disease, pp. 94-132, 185-243, Churchill Livingstone, Edinburgh, 1982

O'Rourke MF, Avolio AP, Lauren PD, Y ong J. Age related changes of elastic lamellae in the human thoracic aorta. Journal of the American College of Cardiology 9: 53A, 1987

O'Rourke MF, Avolio AP. Pulsatile flow and pressure in human systemic arteries: studies in man and in multibranched model of the human systemic arterial tree. Circulation Research 46: 363-372, 1980

Rutan GH, Kuller LH, Neaton JD, et al. Mortality associated with diastolic hypertension and isolated systolic hypertension among men screened for the Multiple Risk Factor Intervention Trial. Circulation 77: 504-514, 1988

Safar ME, London GM. Arterial and venous compliance in sus­tained essential hypertension. Hypertension 10: 133-139, 1987

Safar ME, Laurent S, Pannier BM, London GM. Structural and functional modifications of peripheral large arteries in hyper­tensive patients. Journal of Clinical Hypertension 3: 360-367, 1987

Safar ME, Simon AC, Levenson JA, Cazor JL. Hemodynamic effect of di1tiazem in hypertension. Circulation Research 52 (Supp!. I): 169-173, 1983

Safar ME, Simon AC. Hemodynamics in systolic hypertension. In Zanchetti A, Tarazi RC (Eds) Pathophysiology of hyperten­sion, cardiovascular aspects. Handbook of Hypertension, Vol. 7, pp. 225-241, Elsevier, Amsterdam, 1986

Schulman SP, Weiss JL, Becker LC, et a!. The effects of anti­hypertensive therapy on left ventricular mass in elderly patients. New England Journal of Medicine, 322: 1350-1356, 1990

Tverdal A. Systolic and diastolic blood pressure as predictor of coronary heart disease in middle-aged Norwegian men. British Medical Journal 294: 671-673, 1987

Van Merode T, Van Bortel L, Smeets FA, et a!. The effect of verapamil on carotid artery distensibility and cross-sectional compliance in hypertensive patients. Journal of Cardiovas­cular Pharmacology 15: 109-103, 1990

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Wolinsky H. Long term effects of hypertension on rat aortic wall and their relation to concurrent aging changes: morphological and chemical studies. Circulation Research 30: 301-309, 1972

Correspondence and reprints: Dr Gerard London. Centre Hos­pitalier Manhes, 91700 Fleury-Merogis, France.

Discussion

Prof A. Zanchetti: If we compare clinical blood pressure with ambulatory blood pressure, clinical blood pressure increases with age (as expected), but the increase in ambulatory blood pressure is much smaller. Do you think that ambulatory blood pres­sure does not measure the reflected wave, or that in a quieter setting there is less reflected wave, or that the wave is reflected more slowly in this set­ting? Perhaps, in the elderly, there is a large com­ponent of white coat hypertension that is depend­ent on the velocity of the reflected wave.

Dr G. London: In older subjects there is not much difference between central aortic blood pres­sure and peripheral blood pressure, so I think that the white coat effect exists for reasons other than the reflected wave. In contrast, in young patients the pressure measured at peripheral sites is not rep­resentative of the pressure at central sites and this is especially true during exercise. For example, in a 20-year-old the pressure amplification between brachial and aortic pressures is about 20 to 30%, and during ex~rcise it could be 50 to 60%. In older patients, the stiffness of the arteries makes the pulse wave velocities high and the return 'ofthe reflected wave is very rapid. Therefore, there is summation at all levels of the arteries.

Prof Zanchetti: When blood pressure is meas­ured in the clinic, does the higher sympathetic tone decrease compliance, causing an increased re­flected wave and a higher systolic blood pressure?

Prof London: Absolutely. During stress, the pulse wave velocity increases much more in older patients than in young subjects, so the delay in wave reflection is shortened. .