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(Hypertension. 1995;26:531-534.)
© 1995 American Heart Association, Inc.

Articles

Effects of Antihypertensive Agents on Local Arterial Distensibility and Compliance

Luc M. Van Bortel; Mirian J. Kool; Harry A. Struijker Boudier

From the Department of Pharmacology, Cardiovascular Research Institute Maastricht, University of Limburg, Maastricht, Netherlands.

Correspondence to Luc M. Van Bortel, Department of Pharmacology, Cardiovascular Research Institute Maastricht, University of Limburg, PO Box 616, 6200 MD Maastricht, Netherlands. E-mail l.vanbortel@farmaco.rulimburg.nl.

	Abstract

Top Abstract Introduction Echo Tracking Techniques for... Effect of Antihypertensive Drugs... Factors Influencing the Effects... References

 
Abstract Distensibility and compliance are important vessel wall properties. Distensibility is related to elastic properties of the arterial wall, and compliance reflects the buffering function of the artery. Distensibility is a determinant of stress on the vessel wall. A decreased distensibility might increase the risk of arterial wall damage. Therefore, a preserved local distensibility might be important in protecting the arterial wall of each particular artery and especially of those arteries that are more susceptible to vascular disease. Local distensibility and compliance of various large arteries can be measured noninvasively with echo tracking techniques. Studies on local distensibility and compliance revealed that with the calcium antagonist verapamil and the angiotensin-converting enzyme inhibitor perindopril arterial compliance increased mainly because of an increase in distensibility, with only a minor effect on arterial diameter. In contrast, the nitrate compound isosorbide dinitrate increased compliance mainly by increasing arterial diameter, without an increase in distensibility. This indicates that an increase in arterial compliance does not automatically imply an increase in arterial distensibility. The effect of antihypertensive drugs may also depend on the vascular territory. The diuretic amiloride/hydrochlorothiazide increased brachial artery compliance but not common carotid artery compliance. During angiotensin-converting enzyme inhibition the effect on arterial compliance was smaller at the carotid than the femoral artery. However, the opposite held for the nitrate compound. These distinctive effects of antihypertensive drugs on arterial distensibility and compliance and on vascular territories may be relevant to pharmacological prevention and management of arterial disease.

Key Words: antihypertensive agents • compliance • arteries

	Introduction

Top Abstract Introduction Echo Tracking Techniques for... Effect of Antihypertensive Drugs... Factors Influencing the Effects... References

 
Distensibility and compliance are important vessel wall properties. Compliance is defined as the change in volume per unit of pressure (V/P) and reflects the buffering function of the vessel.^{1 2} Arterial compliance is an important determinant of the afterload on the heart¹ ; a decrease in total arterial compliance contributes to a higher afterload. Arterial compliance (C) is related to arterial distensibility (D) and arterial volume (V) by the formula C=DxV.² Distensibility, defined as the relative change in volume per unit of pressure ([V/V]/P), is related to the elastic Peterson modulus³ and is considered a determinant of stress on the vessel wall. It has been suggested that a decreased distensibility might increase the risk of arterial wall damage, an important feature in atherosclerotic disease.⁴ As a consequence, preserved local vessel wall properties might be important in protecting the arterial wall at that particular site of the artery. A recent study⁵ investigating the effect of insulin-dependent diabetes on local arterial wall properties provided more evidence for such a relation between decreased arterial distensibility and arterial disease. It is known that in diabetics early stages of atherosclerosis occur in the femoral artery.⁶ In the study on uncomplicated insulin-dependent diabetics, distensibility of the femoral artery was decreased, whereas distensibility and compliance of the carotid and brachial arteries were not altered.⁵

Studies on local arterial wall properties also revealed that large conduit arteries do not react similarly to disease states and to changes in physiological conditions. In hypertension, distensibility and compliance of elastic arteries decrease.⁷ However, compliance of the radial artery does not decrease, probably compensating for the loss of compliance in elastic arteries.⁸ Aging decreases elasticity of the common carotid artery,^{9 10} but such an effect was not found in the femoral artery.⁹ From these observations it also appears that local distensibility and compliance may offer clinically relevant information.

This article describes the strength and pitfalls of the echo tracking method of measuring local compliance and discusses new insights obtained with this technique about the effect of antihypertensive drugs on arterial distensibility and compliance.

	Echo Tracking Techniques for Measurement of Local Vessel Wall Properties in Humans

Top Abstract Introduction Echo Tracking Techniques for... Effect of Antihypertensive Drugs... Factors Influencing the Effects... References

 
In humans, different aspects of arterial wall properties can be measured, such as total, regional, and local compliance. Total arterial compliance (C) of the arterial tree has been estimated from stroke volume (SV) and pulse pressure (PP) by the formula PP=SV/C.¹¹ However, this formula is incomplete, because apart from the compliance of large vessels and stroke volume, other factors, such as early reflected pulse waves,^{12 13 14} can influence pulse pressure. Recently, new approaches for the measurement of total arterial compliance are being proposed. Regional compliance, which describes compliance in an arterial segment, can be calculated from arterial volume and distensibility. Regional distensibility is mainly measured with the use of pulse wave velocity. Distensibility and pulse wave velocity are inversely related.³ In the literature pulse wave velocity regularly has been mentioned as a measure of arterial compliance instead of distensibility. Arterial volume is more difficult to assess because vascular diameter is not constant over the arterial segment.

Local distensibility and compliance can now be assessed by new echo tracking techniques.^{15 16} Echo tracking devices can measure quite accurately diameter (d) and the stroke change in diameter (d) of various large arteries. Assuming that during the heart cycle arteries predominantly change in diameter and not much in length, cross-sectional compliance (CC), defined as arterial compliance per unit of length (L), can be used as an estimate of local compliance. Cross-sectional compliance is the change in cross-sectional area of the vessel (A) per unit of pressure: CC=[V/L]/P=A/P= · d · d/(2 · P). Similarly, the distensibility coefficient (DC) can be defined as the relative change in cross-sectional area of the vessel (A/A) per unit of pressure: DC=[A/A]/P=2 · d/d/P.

These formulas show that cross-sectional compliance and the distensibility coefficient can be calculated from arterial diameter, stroke change in diameter, and pulse pressure. Compared with other techniques, the strength of these echo tracking techniques is that both distensibility and compliance can be calculated and different arterial territories can be investigated. Although the method accurately measures diameter and stroke change in diameter, the weakness of this method is that accurate noninvasive assessment of pulse pressure at the site of the arterial wall movement registration might sometimes be difficult. In contrast to mean arterial pressure, pulse pressure is not equal in large arteries.¹² As a consequence, the use of pulse pressure in one artery as a surrogate for pulse pressure in the target artery might be erroneous. However, if a good relation between pulse pressures in target and surrogate arteries exists, the error may be proportional. Consequently, despite incorrect absolute values of distensibility and compliance, results of comparative studies may demonstrate quite accurately changes in vessel wall properties if pulse pressures in target and surrogate arteries behave similarly in different conditions. Table 1 shows that the behavior of noninvasively measured pulse pressure at the finger artery (Finapres, TNO Instruments) can differ from the behavior of pulse pressure at the brachial artery (Dinamap, Critikon). As expected for a smaller, more peripheral artery,^{9 12} finger pulse pressures were higher than brachial artery pulse pressures. But is this difference in pulse pressure constant? During smoking¹⁷ Finapres pulse pressure increased by 16%, and Dinamap pulse pressure did not change statistically. Also, for a similar Dinamap pulse pressure, Finapres pulse pressure was significantly higher in diabetics.⁵ Although device errors cannot be fully excluded, these data strongly suggest a disparate behavior of finger and brachial artery pulse pressures in different conditions. As a consequence, the use of finger pulse pressure as a surrogate for brachial artery pulse pressure can lead to faulty conclusions on arterial distensibility and compliance in these conditions.

View this table: [in this window] [in a new window]   Table 1. Blood Pressure Measured at the Finger and Brachial Arteries Before and After One Cigarette and in Uncomplicated Insulin-Dependent Diabetics and Matched Control Subjects

Another example is the relation between brachial and carotid artery pulse pressures. Although a good relation has been described between brachial and carotid artery pulse pressures,¹⁸ the use of brachial artery pulse pressure as a surrogate for carotid artery pressure may also lead to faulty conclusions, particularly in the presence of early reflected pulse waves. These early reflected pulse waves may boost pulse pressure in the ascending aorta and carotid artery but not in the brachial artery¹³ and may disturb the relation between brachial and carotid artery pulse pressures. To overcome these problems, researchers recently have proposed assessing pulse pressure with applanation tonometry.¹⁹ Alternatively, calculation of the pulse pressure of a central artery with the amplitude and contour of the pressure wave of a peripheral artery may also be promising.²⁰

	Effect of Antihypertensive Drugs on Local Arterial Distensibility and Compliance

Top Abstract Introduction Echo Tracking Techniques for... Effect of Antihypertensive Drugs... Factors Influencing the Effects... References

 
The effects of different antihypertensive drugs on large artery compliance have been reviewed recently.²¹ Since these effects have been studied with different techniques, they are not limited to effects on local compliance and are beyond the scope of this article. Therefore, only the effects of first- and second-choice (as defined in JNC V²² ) antihypertensive drugs are briefly mentioned. Angiotensin-converting enzyme (ACE) inhibitors, calcium antagonists, most selective ß₁-blockers, and ß-blockers with vasodilating properties improved large artery compliance, whereas nonselective ß-blockers did not.²¹ Studies on diuretics have not been conclusive.^{21 23} Since large artery properties are inversely related to mean arterial pressure,²⁴ a reduction in blood pressure may improve large artery compliance by itself without a direct effect of the drug on large artery compliance. In a comparative study, for a similar decrease in blood pressure, the increase in large artery compliance was more pronounced with the ACE inhibitor perindopril than with the combined diuretic amiloride/hydrochlorothia- zide,²³ which might suggest a direct effect of the ACE inhibitor on large artery compliance.

With the use of echo tracking techniques, both local distensibility and compliance can be measured at different arterial territories. Since arterial compliance is related to arterial distensibility and volume,² local cross-sectional compliance can increase by an increase in distensibility and/or in arterial diameter. The increase in compliance during calcium antagonism (verapamil²⁵ ) and ACE inhibition (perindopril²³ ) was mainly caused by an increase in distensibility, with a minor influence on large artery diameter. The diameters of the common carotid and brachial arteries even decreased during long-term ACE inhibition (Table 2), probably because of the lower distending pressure. Isosorbide dinitrate increased the compliance of the carotid and brachial arteries²⁶ mainly through an increase in large artery diameter. In normotensive subjects, distensibility did not increase with isosorbide dinitrate. Although the number of studies investigating the effect of antihypertensive drugs on local arterial distensibility and compliance is limited, these studies show a disparate effect of antihypertensive drugs on these two principal arterial wall properties. They indicate that an increase in arterial compliance does not automatically imply an increase in arterial distensibility. If the concept is true that a lower distensibility might represent a higher risk of arterial damage and arterial disease, then the effects of isosorbide dinitrate may be less favorable to the arterial wall than the effects of other antihypertensive agents such as ACE inhibitors and calcium antagonists.

View this table: [in this window] [in a new window]   Table 2. Percent Changes in Vessel Wall Parameters With Perindopril and Isosorbide Dinitrate

The effect of antihypertensive agents may also depend on the vascular territory. The diuretic amiloride/hydrochlorothiazide did not change carotid artery wall properties but did increase brachial artery wall properties.²³ During ACE inhibition the percent change in compliance from baseline was markedly higher (descriptive analysis) in the brachial and femoral arteries than in the common carotid artery (Table 2). However, in patients with early reflected pulse waves, pulse pressure may decrease more in the carotid artery than in the brachial artery because of the disappearance of these early reflected pulse waves during ACE inhibition.¹³ This may lead to an inaccurate assessment of the change in pulse pressure and to an underestimation of the effect of the ACE inhibitor on distensibility and compliance of the carotid artery. However, even if distensibility and compliance of the carotid artery were underestimated, the differences between the femoral and brachial arteries in Table 2 are not likely to disappear. In contrast to the ACE inhibitor, the nitrate compound appeared to have the smallest effect on femoral arterial parameters, whereas the percent change in diameter was similar in the common carotid and brachial arteries (Table 2). Other authors²⁷ investigating the short-term effect of isosorbide dinitrate in hypertensive patients found a remarkably similar effect on arterial diameter: The increase in diameter was 12% in the carotid artery and 9% in the brachial artery and did not reach statistical significance in the femoral artery. The effect on compliance was larger in the hypertensive than in the normotensive individuals (Table 2). However, the pattern was identical: The smallest effect was seen in the femoral artery (+21%), and the largest increase in compliance was observed at the brachial artery (+147%), with an intermediate effect on the common carotid artery (+41%).

	Factors Influencing the Effects of Antihypertensive Agents on Large Artery Properties

Top Abstract Introduction Echo Tracking Techniques for... Effect of Antihypertensive Drugs... Factors Influencing the Effects... References

 
Apart from the nature of the antihypertensive drug and the investigated vascular territory, the drug dose might be important. For example, at higher doses selective ß₁-blockers may lose selectivity. This might explain the lack of increase in compliance in some studies^{28 29} on selective ß₁-blockers.

Apart from the nature of the diuretic, differences in the duration of treatment might be responsible for the disparate results of studies on diuretics. After short-term treatment (6 weeks) diuretics did not increase large artery compliance,^{30 31} whereas another study demonstrated an increase in brachial artery compliance after 6 months of treatment.²³

With age, structural changes cause a decrease in distensibility and compliance of the carotid artery. These structural changes may be responsible for an altered effect of antihypertensive drugs in the elderly. For example, despite a larger fall in blood pressure, vessel wall properties were less increased in elderly (60 years) than in young (40 years) hypertensive patients with 120 mg verapamil three times daily.¹⁴

To summarize, the effect of antihypertensive agents on large artery properties may depend on such factors as the nature and dose of the drug used, the decrease in blood pressure, the duration of treatment, the arterial state (aging and disease), and the vascular territory.

In conclusion, measurement of local distensibility and compliance has brought us new insights into the reactions of large conduit arteries to disease states and changes in physiological conditions. The small number of studies investigating the effect of antihypertensive drugs on local arterial distensibility and compliance have revealed (1) that an increase in arterial compliance does not automatically imply an increase in arterial distensibility and (2) that the effect of the drug may depend on the vascular territory. These distinctive effects of antihypertensive drugs on arterial wall properties may be relevant to the pharmacological prevention and management of arterial disease. Therefore, investigation of the effects of various classes of antihypertensive drugs on the wall properties of different arterial sites should be advocated, especially of those arteries that are prone to arterial disease.

	References

Top Abstract Introduction Echo Tracking Techniques for... Effect of Antihypertensive Drugs... Factors Influencing the Effects... References

 

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This Article Abstract Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Van Bortel, L. M. Articles by Struijker Boudier, H. A. Search for Related Content PubMed PubMed Citation Articles by Van Bortel, L. M. Articles by Struijker Boudier, H. A.