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(Hypertension. 1995;25:327-334.)
© 1995 American Heart Association, Inc.

Articles

Lisinopril Improves Aortic Compliance and Renal Flow

Comparison With Nifedipine

Hiroyuki Shimamoto; Yoriko Shimamoto

From the Department of Cardiovascular Medicine, PIA Nakamura Hospital, Hiroshima, Japan.

Correspondence to Hiroyuki Shimamoto, MD, 2-24-1, Koi-Higashi, Nishi-ku, Hiroshima 733, Japan.

	Abstract

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Abstract We compared the systemic and regional hemodynamic effects of nifedipine and lisinopril in 26 elderly hypertensive patients with the use of the pulsed Doppler ultrasound technique. Nifedipine is a dihydropyridine calcium antagonist, and lisinopril is an angiotensin-converting enzyme inhibitor. The study had a single-blind crossover design: nifedipine and lisinopril were given for 8 weeks each after washout periods of 4 weeks. Both nifedipine and lisinopril significantly reduced mean arterial pressure to the same extent (P<.01); cardiac output remained unchanged in both nifedipine- and lisinopril-treated groups. Lisinopril increased renal flow significantly (P<.01), but nifedipine did not. Common carotid, vertebral, celiac, and superior mesenteric arterial and diaphragmatic and terminal aortic flows did not show a significant change with either nifedipine or lisinopril. The specific action of lisinopril on the thoracic aorta was a marked improvement of aortic compliance compared with nifedipine, which might be partly responsible for an increase in renal flow. Lisinopril may provide more desirable regional hemodynamic effects and additional benefits for elderly hypertensive patients.

Key Words: nifedipine • hemodynamics • Doppler flowmetry • compliance

	Introduction

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In older patients, hypertension is a prevalent problem, with significant morbid consequences including cerebrovascular, cardiac, renal, and peripheral vascular diseases. Because recent studies have established a firm rationale for drug therapy in this population and therapeutic developments have made effective treatment possible, it is essential in the clinical field to decide which of the available antihypertensive agents can effectively treat older individuals. In addition to diuretics¹ and ß-blockers,² calcium antagonists and angiotensin-converting enzyme (ACE) inhibitors may also be appropriate as first-line monotherapy for elderly hypertensive patients, although insufficient long-term data have been available to evaluate the ability of these agents to protect against stroke and other cardiovascular complications.

Hemodynamically, the primary disturbance in essential hypertension is an increase in total peripheral resistance.³ Resistance often differs in individual vascular beds, and the responses of individual blood vessels to antihypertensive agents can be qualitatively and quantitatively different; yet when total peripheral resistance is being calculated, these responses are averaged. Because two major goals of antihypertensive treatment are decreases in elevated regional vascular resistances and maintenance of adequate regional blood flows, measurements of regional blood flow are mandatory. It is unfortunate, however, that regional blood flow measurements in previous human studies of antihypertensive agents have been restricted to one or only a few organ systems.

On the other hand, because the aorta becomes progressively less distensible with advancing age, aortic compliance, which can be estimated from pulse-wave velocity, becomes more important to systemic and regional hemodynamics. Furthermore, it has been reported that calcium antagonists⁴ and ACE inhibitors⁵ exert a beneficial action on compliance of large arteries for the treatment of hypertension associated with atherosclerotic disease.

This study was designed to compare the effects of nifedipine and lisinopril on hemodynamics and aortic compliance in elderly hypertensive patients because the recent development of the pulsed Doppler ultrasound technique has provided a noninvasive, quantitative method of examining flows in cardiac chambers and various regional arteries.^{6 7} Nifedipine is a dihydropyridine calcium antagonist with little or no effect on the slow calcium channels involved in myocardial conduction or contractility; its action in preventing the influx of calcium into smooth muscle cells is manifested primarily as a vasodilator effect on peripheral blood vessels. Lisinopril, a new, long-acting ACE inhibitor, is a lysine derivative of enalaprilat that has an antihypertensive profile similar to that of enalapril. Unlike enalapril, however, lisinopril is not a prodrug and thus does not require hepatic activation to produce ACE inhibition.

	Methods

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Subjects
Twenty-six patients (10 men and 16 women; mean age, 69.6±6.8 years) with essential hypertension (World Health Organization stage I or II) were studied. Patients with bruits, ischemic attacks, completed strokes, or limb ischemia were excluded from the present study. Hypertension was defined as blood pressure measurements of at least 160 mm Hg systolic or 90 mm Hg diastolic on three subsequent readings after discontinuation of all medication for 4 weeks or longer. All subjects showed normal sinus rhythm. The cause of hypertension was not found in any of the patients. The study was approved by the institutional review committee of PIA Nakamura Hospital. After the nature and purpose of the study were explained, informed consent was obtained. The procedures followed were in accordance with institutional guidelines.

Studies
The present study had a single-blind crossover design: lisinopril was given once daily, and sustained-release nifedipine was administered twice daily for 8 weeks each, both after washout periods of 4 weeks each. The initial dose of nifedipine or lisinopril was 10 mg/d each; these doses were increased to a maximum of 30 mg/d for both nifedipine and lisinopril to achieve a reduction in mean arterial pressure of 10 mm Hg or more. All hemodynamic and laboratory studies were performed at the end of each washout period and active treatment period.

In our preliminary study, 16 patients with essential hypertension were randomized to either lisinopril (n=8) or nifedipine (n=8). All the patients either had never been treated before or had not been treated in more than 1 year. All hemodynamic indexes used in the present study were measured every week during treatment. These indexes reached a steady level in 8 weeks; that is, there was no significant difference in these hemodynamic indexes between the 7- and 8-week treatments. Subsequently, in the washout periods, we measured all hemodynamic and hormonal parameters every week. These parameters returned to the control values within the 4-week washout period. Thus, we chose an 8-week treatment period and a 4-week washout period for the present study.

Hemodynamic Measurements
All studies were performed while patients were in a supine position and a postabsorptive state between 11 AM and noon after a 30-minute rest. Room temperature was held constant between 20° and 23.5°C. Three sets of blood pressure tests were taken in both arms simultaneously by the same three observers who used conventional sphygmomanometers with a mercury column according to the official recommendation of the American Heart Association.⁸ Mean arterial pressure was calculated as the sum of diastolic blood pressure plus one third of pulse pressure.

Ultrasound studies used commercially available phased-array echocardiographic-Doppler systems (U-sonic model RT5000 or RT8000, Yokogawa Medical Systems). Systemic hemodynamic data were measured by pulsed Doppler echocardiography and were used to determine cardiac output.⁷ Total peripheral resistance was calculated by dividing mean arterial pressure by cardiac output.

Common carotid, vertebral, celiac, superior mesenteric and renal arterial and diaphragmatic and terminal aortic flows were determined by use of the following formula:

where 0.59 is the ratio of regional arterial flow measured by an electromagnetic flowmeter to that measured by the pulsed Doppler technique; Int_i is the regional flow velocity–time integral; and D_i is the diameter of each peripheral artery determined by B-mode scan at the time of systolic peak flow velocity (Figs 1, 2, and 3). In our previous study,⁶ during surgery regional arterial flows were measured by a Doppler method and by electromagnetic flowmeter. Comparison of simultaneous blood flow measurements indicated an excellent correlation between these two methods (r=.93, n=84):

View larger version (118K): [in this window] [in a new window]   Figure 1. Measurements of parameters from Doppler ultrasound flow signals in the common carotid (top) and vertebral (bottom) arteries. Shown are two-dimensional images (left) and electrocardiographic (ECG) and Doppler ultrasound tracings (right). Left, Sampling volume for Doppler ultrasound measurement is indicated. Right, Dots of the Doppler ultrasound flow signal show instantaneous mean flow velocity. The flow velocity–time integrals in systole (S) and diastole (D) are measured by a planimeter. TOWARD indicates flow components toward the transducer; AWAY, flow components away from the transducer.

View larger version (103K): [in this window] [in a new window]   Figure 2. Measurements of parameters from Doppler ultrasound flow signals in the celiac (top), superior mesenteric (middle), and renal (bottom) arteries. Shown are two-dimensional images (left) and electrocardiographic (ECG) and Doppler ultrasound tracings (right). See Fig 1 legend for details and definitions.

View larger version (105K): [in this window] [in a new window]   Figure 3. Measurements of parameters from Doppler ultrasound flow signals in the diaphragmatic (top) and terminal (bottom) aortas. Shown are two-dimensional images (left) and electrocardiographic (ECG) and Doppler ultrasound tracings (right). See Fig 1 legend for details and definitions.

As flow was measured at the bilateral arteries, common carotid, vertebral, and renal arterial flows were calculated as the sum of bilateral flows. Regional vascular resistances were obtained by dividing the mean arterial pressure by regional vascular flows.

Regional flow–velocity time integrals were determined by planimetric measurement of each flow-velocity curve; one was the integral in systole, and the other was the integral in diastole. The ratio of diastole to systole (D/S) of each regional flow was calculated. Since the flow-velocity curve was recorded at the bilateral arteries, both D/S values were averaged in the common carotid, vertebral, and renal arteries. As to the D/S of the thoracic aorta, according to the Windkessel model, as the aorta becomes more compliant, more of the stroke volume ejected by the left ventricle is considered to be stored in the elastic aorta, resulting in less forward arterial flow in systole and more forward flow in diastole.

Determination of Pulse-Wave Velocity
Pulse-wave velocity (PWV) was obtained by dividing the aortic distance by the delay time between the simultaneously recorded aortic flow pulses. Doppler flow recordings were taken at two sites simultaneously: the aortic valve and the descending thoracic aorta at the diaphragm. For aortic valve flow, the transducer was placed at the apical impulse, and the apical long-axis view of the left ventricle was imaged. For diaphragmatic aortic flow, the transducer was positioned on the skin between the xyphoid process and the umbilicus. Transcutaneous Doppler flow waves were recorded at high speed (100 mm/s) with a strip-chart recorder (U-sonic Line Scan Recorder SR-02 Yokogawa Medical Systems). The transit time was obtained from the foot-to-foot delay between the flow waves. The point at which the sharp systolic upstroke began was identified as the "foot" of the wave. Transit times for 10 beats were averaged and designated to be t, the time required for the pulse to travel between the recording sites (Fig 4).

View larger version (112K): [in this window] [in a new window]   Figure 4. Measurements of pulse-wave velocity by two-dimensional images (left) and Doppler and electrocardiographic (ECG) tracings (right). Sampling volume for Doppler measurement is placed at two sites simultaneously: the aortic valve (top) and the descending thoracic aorta at the diaphragm (bottom). The transit time (t) is obtained from the foot-to-foot delay between the flow waves. LV indicates left ventricle; LA, left atrium; and Ao, aorta.

The aortic distance (x) between the aortic valve and the descending aorta at the diaphragm was measured by nuclear magnetic resonance imaging in the long-axis view (Resona, Yokogawa Medical Systems; Fig 5) or by computed tomographic reconstruction imaging in the long-axis view (Image Max II, Yokogawa Medical Systems; TCT-300/EZ, Toshiba Medical Systems). PWV was determined to be x (centimeters) divided by t (seconds).

View larger version (146K): [in this window] [in a new window]   Figure 5. Measurement of pulse-wave velocity by nuclear magnetic resonance imaging (long axis). The distance between the aortic valve and the descending aorta at the diaphragm is measured.

Humoral Measurements
Plasma norepinephrine and epinephrine were measured by an electrochemical method with high-performance liquid chromatography.⁹ Plasma renin activity was measured by radioimmunoassay of the angiotensin I (Ang I) generated at pH 6.0 with use of a kit with ¹²⁵I-angiotensin ( Coatrenin, Baxter) according to the method of Ogihara et al.¹⁰ Plasma Ang II was measured by radioimmunoassay with the Florisil (magnesium silicate) absorption method.¹¹ Plasma atrial natriuretic peptide (ANP) was determined by immunoradiometric assay by an ANP IRMA kit (Shionoria ANP, Shionogi).¹²

Statistics
Data are expressed as mean±SD. The Wilcoxon matched-pairs signed-rank test was used for comparison. A value of P<.05 was considered statistically significant.

To identify determinants of PWV, stepwise multiple linear regression computations were performed. The change in PWV with lisinopril was used as the dependent variable. We used changes in cardiac output, regional blood flows, and D/S in regional vascular beds as potential independent variables, and we analyzed all subjects. Furthermore, the significance of possible determinants of changes in plasma ANP and the changes in plasma ANP were evaluated by stepwise multiple linear regression analysis. Changes in cardiac output, regional blood flows, and D/S of regional blood flows were assessed as possible determinants of changes in ANP.

	Results

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The 26 patients were randomly allocated to take either nifedipine (n=13) or lisinopril (n=13) as the first active drug. There were no significant differences between systemic and regional parameters and laboratory data in the washout period before nifedipine or lisinopril.

Systemic Hemodynamics
Both nifedipine and lisinopril reduced mean arterial pressure significantly (average dose, 20.4 and 18.2 mg/d, respectively). Neither the patients who received nifedipine nor those who received lisinopril showed a significant change in heart rate. Systolic, diastolic, and mean arterial pressures and total peripheral resistance were significantly decreased to the same extent with nifedipine (all P<.01) versus lisinopril (all P<.01). Although cardiac output remained unchanged with nifedipine and lisinopril, the increase in cardiac output was greater with nifedipine than lisinopril (P<.05). For further information on systemic hemodynamics, see Table 1.

View this table: [in this window] [in a new window]   Table 1. Central Hemodynamics Before and After Treatment

Regional Hemodynamics
Both carotid and vertebral arterial flows remained unaltered during treatment with nifedipine and lisinopril. Nifedipine increased carotid and vertebral arterial flows to a greater extent than lisinopril (both P<.05). Lisinopril increased renal flow significantly (P<.01), but nifedipine did not. The celiac and superior mesenteric arterial and the diaphragmatic and terminal aortic flows did not show a significant change with either nifedipine or lisinopril.

All regional vascular beds showed a significant decrease in regional vascular resistance in both the nifedipine- and lisinopril-treated groups. D/S, which reflects the proportion of diastolic to systolic flow, increased in the renal artery and diaphragmatic aorta in patients treated with lisinopril. In the lisinopril group, a significant relation existed between the change in D/S (D/S) of diaphragmatic aortic flow and that of renal flow (n=26, r=.72, P<.01, Fig 6):

View larger version (18K): [in this window] [in a new window]   Figure 6. Scatterplot shows relationship between change in ratio of diastolic to systolic flow (D/S) of diaphragmatic aortic (Diaph Ao) and that of renal arterial flow (r=.72, n=26, P<.01).

Although D/S remained unchanged in the lisinopril-treated patients in all regional vascular beds other than in the renal artery and diaphragmatic aorta, an increase in D/S of terminal aortic flow was greater with lisinopril than with nifedipine (P<.05). Nifedipine had no effect on D/S of any regional flow.

Both nifedipine and lisinopril decreased PWV significantly (both P<.01). The decrease in PWV was greater with lisinopril than with nifedipine (P<.01). For further information on regional hemodynamics, see Table 2.

View this table: [in this window] [in a new window]   Table 2. Regional Hemodynamics Before and After Treatment

Hemodynamic Variables That May Determine the Change in PWV With Lisinopril
We tested the changes in cardiac output, regional blood flows, and D/S of regional vascular flows as potential independent variables with lisinopril. However, only the change in D/S of diaphragmatic aortic flow was independently correlated with the dependent variable (the change in PWV).

The final regression equation (n=26, r=-.63, P<.01, Fig 7) was

View larger version (18K): [in this window] [in a new window]   Figure 7. Scatterplot shows relationship between change in ratio of diastolic to systolic flow (D/S) of diaphragmatic aortic (Diaph Ao) flow and change in pulse-wave velocity (r=-.63, n=26, P<.01).

Laboratory Data
Nifedipine had no effect on laboratory parameters. Lisinopril decreased ANP significantly (P<.05). Stepwise multiple linear regression analysis revealed that only the change in cardiac output was independently correlated with the change in ANP (n=26, r=.64, P<.01, Fig 8):

View larger version (18K): [in this window] [in a new window]   Figure 8. Scatterplot shows relationship between change in cardiac output and change in atrial natriuretic peptide (ANP) (r=.64, n=26, P<.01).

Other potential independent variables, such as the changes in regional blood flows and those in the D/S of regional vascular flows, showed no significant correlation with the dependent variable (the change in ANP).

There was no significant change in the other humoral parameters, including plasma renin activity, Ang II, or aldosterone in patients given lisinopril; the reduction in mean arterial pressure was not significantly related with either baseline plasma renin activity or the change in plasma renin activity. Table 3 summarizes the laboratory data.

View this table: [in this window] [in a new window]   Table 3. Laboratory and Hormonal Parameters Before and After Treatment

	Discussion

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In the present study, we assessed hemodynamic responses to two different kinds of vasodilating agents, nifedipine and lisinopril, which decreased mean arterial pressure and total peripheral resistance to the same extent. Nifedipine had no significant effects on any of the regional flows. Lisinopril increased renal arterial flow significantly but did not alter blood flow in any other regional vascular bed. The specific action of lisinopril on the thoracic aorta was a marked improvement of aortic compliance compared with nifedipine, which might be partly responsible for an increase in renal flow. The clinical evidence and the rationale for this conclusion are discussed below.

Systemic Hemodynamics
The blood pressure–lowering effect of nifedipine was similar to that of lisinopril in this study, which is consistent with other reports demonstrating that the efficacy of both drugs and the proportion of patients responding to treatment were similar in well-controlled studies of 3 and 6 months' duration.^{13 14}

The antihypertensive effects of nifedipine stem from its relaxing action on vascular smooth muscles mainly by inhibiting voltage- and receptor-operated calcium channels.

On the other hand, most of the available data suggest that the beneficial hemodynamic effects of lisinopril are caused by the inhibition of plasma ACE activity and the consequent reduction in Ang II, which directly or indirectly dilates peripheral blood vessels and leads to a reduction in systemic vascular resistance and arterial pressure.¹⁵ In the present study, however, plasma renin activity, Ang II, and aldosterone remained unchanged in patients given lisinopril, as reported previously.^{16 17} Recently, it has also been suggested that inhibition of tissue renin-angiotensin systems contributes to hypotensive responses to lisinopril in such organs as the kidney, vascular tissue, adrenal glands, and brain^{18 19} because the blood pressure response to ACE inhibitors was better correlated with ACE inhibition in the vascular wall than in plasma.^{20 21}

A reduction in arterial pressure induced by these vasodilating agents is expected to augment forward cardiac output if cardiac preload and ventricular contractility remain unchanged. However, in the present study, neither nifedipine nor lisinopril had an effect on cardiac output. Our observations were consistent with previous reports that with nifedipine cardiac output remained unchanged, despite unchanged or increased baroreflex sensitivity.^{22 23} An increment in cardiac output due to a reduction in arterial pressure may be offset by the negative inotropic activity of nifedipine in vivo²⁴ or a reduction in cardiac preload accompanied by venous dilation with nifedipine.²⁵

On the other hand, it has also been reported that with lisinopril treatment cardiac output was decreased²⁶ or remained unchanged.^{27 28} In the present study, lisinopril decreased plasma ANP significantly, as demonstrated in spontaneously hypertensive rats,²⁹ and these changes in plasma ANP significantly correlated with changes in cardiac output. This decrease in ANP indicates a reduction in cardiac filling pressures³⁰ through mechanisms by which lisinopril possesses natriuretic action and venous dilatation^{31 32} because ANP is secreted by the atria under conditions of increased atrial stretch.³³ In addition, lisinopril has a beneficial effect on myocardial contractility, as demonstrated by a 15% increase in the mean velocity of circumferential fiber shortening.¹⁵ The reduction in cardiac output induced by a reduction in cardiac preload may be offset by an increase in cardiac output associated with afterload reduction and the favorable effect on myocardial contractility with lisinopril, resulting in unaltered cardiac output.

Regional Hemodynamics
In patients treated with nifedipine, regional blood flows in cerebral, splanchic, and renal arterial and diaphragmatic and terminal aortic areas were maintained during blood pressure reduction, which led to significant decreases in all regional vascular resistances. These observations suggest that nifedipine acts as a vasodilating agent in all regional vascular beds studied.

In contrast to nifedipine, lisinopril increased renal blood flow significantly during blood pressure reduction, which is consistent with previous findings that long-term treatment with lisinopril (dosage, 5 to 80 mg once per day) significantly increased renal blood flow in patients with essential hypertension.³⁴ Despite pharmacokinetic differences, all ACE inhibitors seem to confer beneficial effects on renal blood flow: an increase in renal blood flow, maintenance or improvement of glomerular filtration rate, and a decrease in urinary excretion of albumin.^{35 36} Furthermore, ACE inhibitors may exert their renal effects even in patients with impaired renal function.³⁷ Inhibition of the local renin-angiotensin system by lisinopril might play an important role in increasing renal blood flow in the present study because lisinopril significantly inhibits renal tissue ACE in both spontaneously hypertensive and normotensive rats.³⁸ On the other hand, regional blood flows in cerebral and splanchic arterial and diaphragmatic and terminal aortic areas remained unchanged, with all their regional resistances decreased.

The estimation of regional resistances used in the present study has an important limitation. As a result of various factors, such as wave reflection, the peripheral arm-cuff blood pressure measurement does not precisely represent the blood pressure in different regional vascular beds. However, this deviation of blood pressure can be minimized by the use of mean blood pressure for this estimation.

Improvement of Aortic Compliance With Lisinopril and Its Effects on Regional Blood Flows
For the study of regional hemodynamics, the importance of arterial compliance should be stressed, especially in elderly hypertensive patients, in whom a loss of elasticity could be caused by intimal and media thickening,³⁹ increased space between the elastic laminae,⁴⁰ active arteriolar constriction, and arterial calcification or atherosclerosis, leading to a decrease in aortic compliance with advancing age. In physiological conditions, large arteries have viscoelastic properties and play the role of a hydraulic filter.⁴¹ Because of the damping effect of large arteries, the periodic flow of the heart is changed into a continuous flow at the capillary level. According to the Windkessel model, the blood begins to flow again in diastole as the compliant walls of the aorta (which expanded during systole) collapse, driving blood at the lower diastolic pressure into the peripheral circulation. Therefore, when the aorta and large arteries become progressively less distensible with advancing age, the ability to absorb pulsations from the ejecting ventricle is reduced.^{42 43} Aortic compliance is a quantitative evaluation of the elasticity of the aorta,^{44 45} and this compliance can be estimated indirectly from PWV. Thus, in the present study, we compared the effects of nifedipine and lisinopril on PWV to analyze the relations between thoracic aortic compliance and regional hemodynamics. As reported previously,⁴⁶ both nifedipine and lisinopril decreased PWV significantly. However, it cannot be concluded from these data that both agents improve compliance of the thoracic aorta. Arterial pressure is also a major determinant of PWV,^{47 48 49} and both agents significantly decreased arterial pressure. Despite similar reductions in arterial pressure, lisinopril decreased PWV more than did nifedipine, which indicates that lisinopril may improve aortic compliance more than nifedipine.

Lisinopril significantly increased the D/S of diaphragmatic aortic flow and of renal arterial flow. Considering that the D/S of diaphragmatic aortic flow is closely correlated with that in PWV, the increase in D/S of diaphragmatic aortic flow might also reflect the improvement of aortic compliance. According to the Windkessel model, as the aorta becomes more compliant, more of the stroke volume ejected by the left ventricle is considered to be stored in the elastic aorta, resulting in less forward arterial flow in systole and more forward flow in diastole.

Moreover, there was also a direct correlation between the change in diaphragmatic aortic and in renal arterial D/S values. These observations suggest that improved aortic compliance by lisinopril leads to increased diastolic flow in the aorta, resulting in an increase in diastolic flow toward the kidney. Therefore, a significant increase in renal flow by lisinopril might be accounted for by improved aortic compliance. However, we cannot rule out the possibility that the renal arteries themselves may become more compliant with ACE inhibition than other vascular beds because effects of Ang II on different vascular beds are nonuniform and the renal vascular bed is especially responsive to the constrictive action of Ang II.⁵⁰

In contrast to lisinopril, nifedipine decreased PWV significantly; however, the D/S remained unchanged in all regional vascular beds during blood pressure reduction with nifedipine. These results indicate that nifedipine does not improve aortic compliance and that a decrease in PWV by nifedipine is primarily due to a reduction in arterial pressure.

O'Rourke⁴⁷ has pointed out that wave reflection could play a part in modifying the pressure and flow contours. The Windkessel model lacks pulse transmission and did not allow us to examine this aspect. In the abdominal aorta, particularly below the renal arteries, a small reverse component can be seen during diastole, and this wave component becomes more marked as the bifurcation is approached under normal conditions. This reverse flow originates in the reflection of the systolic pulse of blood as it travels down the aortic tree and encounters the high impedance of the lower-limb periphery. It is therefore entirely possible that wave reflections can decrease diastolic forward flow in the aorta, leading to a decrease in the D/S. Because the effects of vasodilation on impedance and wave contour are precisely what one would predict from a decrease in peripheral reflection coefficient,⁴⁴ lisinopril may abolish the reverse flow in these large vessels, where reflections occur at the many discontinuities in vascular impedance at the bifurcations of the arterioles, whose muscular tone varies with vasomotor activity. Thus, consideration of wave reflection may prove important if the D/S of diaphragmatic aortic flow and of renal flow can be increased by reduction in wave reflection rather than by increasing aortic compliance through lisinopril. However, nifedipine failed to increase the D/S in all vascular regions, although nifedipine, as well as lisinopril, was expected to dilate large and small arteries equally⁴ and to abolish wave reflections. Thus, the characteristic feature of lisinopril is to cause a preferential improvement of thoracic aortic compliance.

Conclusions
Since an increase in total peripheral resistance is the primary hemodynamic disturbance in essential hypertensive patients, the ideal antihypertensive agent would reduce blood pressure while decreasing regional vascular resistances. Both nifedipine and lisinopril have been shown to fulfill these requirements in elderly hypertensive patients. Hemodynamically, both agents act as vasodilators and maintain regional blood flows during blood pressure reduction. Although the precise mechanism for increasing renal arterial flow and improving aortic compliance with lisinopril is not clear, the effects of ACE inhibition on renal and aortic renin-angiotensin systems clearly play an important role. Lisinopril may provide more desirable regional hemodynamic effects and additional benefits for the elderly suffering from hypertension.

	Acknowledgments

 
This study was supported by Shionogi Co Ltd.

Received July 5, 1994; first decision August 31, 1994; accepted October 25, 1994.

	References

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