Methodological problems in evaluation of cardiovascular effects of stress in humans.

Cardiovascular effects of stress in humans are often assessed by application of physical or emotional stimuli in a laboratory environment. Although this method provides important information, these procedures have several limitations. First, blood pressure and heart rate responses to laboratory stressors are characterized by a limited within-subject reproducibility. Second, there is poor correlation between blood pressure and heart rate responses to different stressors, which implies that individual reaction to stress may be estimated differently according to the test used. Finally, these responses bear only a limited relation to 24-hour or daytime blood pressure variability, that is, they reflect to only a limited extent the tendency of blood pressure to vary during daily activities. If assessed by techniques that allow blood pressure to be continuously recorded for 24 hours in ambulatory subjects, blood pressure variability represents a possible approach to observation of cardiovascular reactivity away from an artificial laboratory environment. However, whether blood pressure variability should be expressed as a percentage or in absolute values is controversial. Furthermore, although naturally occurring stress may markedly increase blood pressure, 24-hour blood pressure variations also depend on factors that are not related to emotional stimuli. Thus, the study of cardiovascular responses to stress in humans encounters several problems, regardless of the method used.

Early 24-hour blood pressure elevation in normotensive subjects with parental hypertension.

Subjects with a family history of parental hypertension are reported to have a slightly higher office blood pressure in the prehypertensive stage. Whether this reflects a hyperreactivity to blood pressure measurement or a more permanent blood pressure elevation, however, is not known. In the present study, blood pressure was measured in 15 normotensive subjects whose parents are both hypertensive (FH++), 15 normotensive subjects with one hypertensive parent (FH(+)-), and 15 normotensive subjects whose parents are not hypertensive (FH--); among the three groups, subjects were matched for age, sex, and body mass index. The measurements were made in the office during a variety of laboratory stressors and during a prolonged resting period, and for a 24-hour period (ambulatory blood pressure monitoring). Office blood pressure was higher in the FH++ group than in the FH-- group (p less than 0.05). The pressor responses to laboratory stressors were similar in the two groups, but the FH++ group had higher prolonged resting and 24-hour blood pressure than the FH-- group; the difference was always significant (p less than 0.05) for systolic blood pressure. The FH++ group also had a greater left ventricular mass index (on echocardiographic examination) than the FH-- group (p less than 0.01). The blood pressure values and echocardiographic values of the FH(+)- group tended to be between those of the other two groups. Thus, the higher blood pressure shown by individuals in the prehypertensive stage with a family history of parental hypertension does not reflect a hyperreactivity to stress but an early permanent blood pressure elevation.(ABSTRACT TRUNCATED AT 250 WORDS)

Ambulatory blood pressure monitoring in the evaluation of antihypertensive treatment.

Cuff blood pressure measurements by doctors and self blood pressure measurements by patients reflect imprecisely 24-hour or daytime mean blood pressure values. This limits the physician's ability to diagnose the absence or presence of hypertension. It also limits his ability to evaluate the response to non-pharmacologic interventions or antihypertensive drugs. This is a major disadvantage because the prognosis of hypertensive persons depends to a large extent on the blood pressure attained during treatment. Ambulatory blood pressure monitoring is a valid method for assessing the effectiveness of antihypertensive treatment because it allows the physician: (1) to determine whether the initially elevated blood pressure is reduced under the various circumstances of the patient's lifetime; and (2) to exclude that this reduction is associated with hypotensive events that might interfere with organ nutrition and function during the day and night. However, this approach has a cost that makes its use impractical in clinical practice, except in cases in which there are reasons to suspect very low or excessively high blood pressures in conditions that are out of the reach of sphygmomanometry. Furthermore, the prognostic value of on-treatment ambulatory blood pressures is still unknown. On the other hand, studies on new antihypertensive agents derive great benefits from the use of ambulatory blood pressure monitoring. This is emphasized by the fact that the ambulatory blood pressure values are more reproducible than isolated cuff blood pressure values, allowing the number of patients necessary to establish an antihypertensive effect to be reduced. Furthermore, these values are little affected by placebo influences thus permitting simplification of the study design. Finally, sequential analysis of the data obtained provides accurate information on the duration of the antihypertensive effect, and thus on the optimal posology to be adopted. However, ambulatory blood pressure monitoring does have technical problems. In the case of non-invasive monitoring, the ability to measure blood pressure phasic events and variability is limited. Another problem, which is of greater importance, is that non-invasive blood pressure monitoring devices generate a number of artifactual and imprecise readings. These problems cannot be entirely eliminated by editing the blood pressure tracing.

Increase in blood pressure reproducibility by repeated semi-automatic blood pressure measurements in the clinic environment.

OBJECTIVE: To evaluate whether increasing the number of blood pressure readings obtained in the clinic environment increases the blood pressure reproducibility. PATIENTS: Thirteen mild essential hypertensive patients studied in the outpatient clinics, following withdrawal of antihypertensive treatment for 4 weeks. METHODS: The systolic and diastolic blood pressures were measured three times, using a mercury sphygmomanometer, with the patient in the sitting position. Measurements were then performed with the patient in the lying position using an oscillometric device (SpaceLabs 90202 or 90207). The device was operated semi-automatically at 3-min intervals until 25 readings had been collected. The same procedure was repeated 4 weeks later. The systolic blood pressure, diastolic blood pressure and heart rate were averaged by considering a progressively greater number of readings, from 1 to 25. The reciprocal of the standard deviation (1/SD) of the mean difference after 4 weeks was taken as the measure of reproducibility. RESULTS: 1/SD increased progressively as the number of semi-automatic blood pressure readings from which the average was calculated increased. For a similar number of blood pressure readings the reproducibility was similar for semi-automatic readings to that for automatic readings obtained by 24-h ambulatory blood pressure monitoring. CONCLUSION: Multiple blood pressure readings obtained semi-automatically in the outpatient clinics increase blood pressure reproducibility and make the value similar to that obtained by ambulatory blood pressure monitoring. The advantage of an increase in reproducibility for studies on antihypertensive drugs thus depends on the number of readings, and can also be obtained by semi-automatic measurements in the clinic environment.

Effect of placebo on 24-h non-invasive ambulatory blood pressure.

Twenty-four-hour mean ambulatory blood pressure has been shown to be devoid of a placebo effect. However, whether this is the case for different periods within the 24 h has not been established. In 27 essential hypertensive outpatients, blood pressure was measured in the doctor's office and by 24-h ambulatory blood pressure monitoring after a 3-week wash-out period from antihypertensive treatment (Control) and following 4 weeks of placebo administration. Office systolic and diastolic blood pressures were reduced by placebo (-9.6 +/- 2.6 and -3.1 +/- 1.7 mmHg, P less than 0.01, respectively), whereas 24-h mean blood pressure values did not show any significant change. This was not the case for all 24-h subperiods, however, because during the initial 8h, systolic and diastolic blood pressures were slightly (-4.1 +/- 9.2 and -2.5 +/- 6.4 mmHg) but significantly (P less than 0.05) lower during placebo than during control. Similar findings were obtained in 14 additional essential hypertensive patients in whom neither placebo nor any other treatment was employed between the two office and 24-h blood pressure measurements. Thus, placebo treatment is associated with a blood pressure reduction in the initial portion of the ambulatory blood pressure profile, probably because of an attenuation of an initial transient alerting response to the procedure. Although so small as to leave the 24-h blood pressure mean unaffected, this may lead to some overestimation of the antihypertensive effect of treatment during an appreciable portion of the circadian blood pressure tracing.

Limited reproducibility of hourly blood pressure values obtained by ambulatory blood pressure monitoring: implications for studies on antihypertensive drugs.

OBJECTIVE: To assess the reproducibility of average hourly blood pressure values obtained by 24-h non-invasive ambulatory monitoring. PATIENTS: Fifteen outpatients with essential hypertension. In all subjects antihypertensive treatment was withdrawn for 4 weeks before and during the 4 weeks of the study. METHODS: The 24-h blood pressure was monitored by a SpaceLabs 5300 device (four readings per hour during the day and three readings per hour during the night) twice, at a 4-week interval. Systolic (SBP) and diastolic blood pressure (DBP) were averaged for each hour and for the whole 24-h period, and hourly and 24-h reproducibility was quantified by the standard deviation of the mean difference (SDD) between the values obtained in the two recordings. RESULTS: The SDD of hourly SBP and DBP was much greater than that of the 24-h values and ranged widely between the hours of recording. The SDD of hourly SBP and DBP were also variably greater than the SDD of the 24-h value in another 14 untreated essential hypertensives in whom 24-h ambulatory blood pressure was monitored intra-arterially twice at a 4-week interval to calculate hourly average blood pressure on thousands rather than on three or four values per hour. CONCLUSION: Reproducibility is less for hourly than for 24-h average blood pressure. This feature (which probably depends on behavioural differences between two recordings) suggests that ambulatory blood pressure measurement partly loses its advantages for reproducibility and reduction in trial size if the results are analysed over hourly periods.

24-hour blood pressure monitoring: evaluation of Spacelabs 5300 monitor by comparison with intra-arterial blood pressure recording in ambulant subjects.

The accuracy of 24-h blood pressure values obtained by ambulatory monitoring via the Spacelabs 5300 device was evaluated by comparison with simultaneous 24-h intra-arterial blood pressure recording from the contralateral arm. The comparison was made in eight essential hypertensive subjects in whom non-invasive blood pressure was measured every 15 (day) or 30 min (night). The measurements were automatically and visually edited to eliminate artefactual readings and hourly and 24-h means were calculated separately for systolic and diastolic blood pressure. The corresponding intra-arterial blood pressure means were also calculated. In the group as a whole, hourly means obtained by the non-invasive device were similar or only slightly different from those recorded intra-arterially. The 24-h systolic blood pressure mean obtained non-invasively was not significantly different from that obtained intra-arterially (138.4 +/- 9.1 and 142.9 +/- 9.2 mmHg, respectively), nor were the corresponding 24-h diastolic blood pressure means significantly different (83.5 +/- 4.5 and 80.6 +/- 3.5 mmHg, respectively). However, in spite of these similarities, there were contrasting and often large discrepancies between non-invasive and intra-arterial values in individual subjects. For the 24-h systolic blood pressure mean the discrepancies ranged from 7.6 +/- 1.1 to 16.1 +/- 2.2 mmHg and for the 24-h diastolic blood pressure mean, from 3.5 to 13.2 mmHg. Thus, the Spacelabs 5300 device has a limited ability to correctly estimate ambulatory blood pressure in individual subjects. It may be better suited for the estimation of group blood pressures, but only because errors are smoothed by the summation of individual errors of opposing signs.

Role of heart rate variability in the production of blood pressure variability in man.

In both normotensive and hypertensive subjects blood pressure (BP) and heart rate (HR) show concordant changes over 24 h. This may depend on a central factor exerting influences of the same nature on cardiac and vascular targets. An alternative explanation, however, is that a cause-effect relationship links these variabilities, i.e. that HR variations induce BP changes [presumably via variations in cardiac output (CO)]. Blood pressure was recorded intra-arterially in five supine and five exercising (walking) essential hypertensive subjects during a control period of 1 h and during an additional hour in which atropine, 0.04 mg/kg body weight, was injected intravenously (i.v.). The same recordings were performed in seven other subjects, in which saline rather than atropine was employed. One-hour BP and HR variabilities (variation coefficients, VC) were computer analysed. In both the supine and the exercising subjects atropine caused a marked reduction in HR VC (-65.3 and -48.4%, respectively). In the supine subjects this reduction was accompanied by only a modest reduction in BP VC whereas in the exercising subjects the BP VC increased by 30.4%. In the seven subjects in which saline was injected no change in BP and HR VC occurred. Thus a marked reduction in HR variability is not accompanied by a comparable attenuation in BP variability, which rules out a cause-effect link between these two phenomena. Indeed, during physical exercise HR stabilization is followed by an increase rather than a reduction in BP variation, which supports the conclusion that under some circumstances HR plays an anti-oscillatory role.

Reproducibility of non-invasive and intra-arterial blood pressure monitoring: implications for studies on antihypertensive treatment.

Ambulatory blood pressure has been shown to be more reproducible than office blood pressure and thus to be more suited for studying the efficacy of antihypertensive drugs. In 34 untreated essential hypertensive subjects, we measured office and 24-h non-invasive or intra-arterial blood pressure twice over a 4-week interval; 24-h intra-arterial blood pressure was obtained by the Oxford method whereas 24-h non-invasive blood pressure was obtained by the automatic SpaceLabs 5300 device, with a 10 min (daytime) or 20 min (night-time) interval between measurements. The standard deviation of the mean difference (s.d.d.) between blood pressures obtained in each recording was taken as the reciprocal of blood pressure reproducibility. The s.d.d. was highest for office blood pressure and for single blood pressure readings taken from 24-h non-invasive recordings. The s.d.d. fell when the two 24-h average non-invasive blood pressures were considered. The fall was progressively greater as the number of ambulatory readings on which the average was calculated increased from two to 24, no further fall being observed when more than 24 values were considered. The maximal reduction in s.d.d. was 59% (systolic) and 42% (diastolic) as compared with the office s.d.d. The two 24-h mean values obtained by the intra-arterial approach were slightly more closely correlated than those obtained non-invasively. However, at comparable sampling rates, the s.d.d. was not substantially lower with 24-h intra-arterial blood pressure and including in the calculation the average of the thousand readings provided by this approach did not cause any further improvement.(ABSTRACT TRUNCATED AT 250 WORDS)

Isobaric compliance of the radial artery is increased in patients with essential hypertension.

OBJECTIVES: Hypertension is known to decrease arterial elasticity and systemic compliance. However, the arterial tree is not a homogeneous system, and whether a distal medium-sized artery such as the radial artery behaves like proximal arteries has not been determined. The aims of the present study were, first, to characterize non-invasively the mechanical properties of the radial artery through the determination of the pressure-diameter curve, the distensibility-pressure curve and the compliance-pressure curve, and, secondly, to compare untreated hypertensive patients with normotensive subjects. METHODS: A new high-precision echo-tracking device was developed which allows the diameter of peripheral arteries to be measured continuously. By relating the changes in internal diameter (cross-sectional changes) to those in blood pressure, the cross-sectional arterial compliance could be determined. PARTICIPANTS: Seventy-eight untreated mild or moderate essential hypertensive patients aged 24-78 years were compared with 44 normotensive subjects aged 22-81 years. In order to increase the database and provide independent assessments of the variables examined, the cross-sectional study was performed independently using a standardized procedure in three different research centres. RESULTS: The major finding was that diameter, distensibility and compliance of the radial artery of hypertensive patients were not significantly different from those of normotensive controls when the two populations were studied at their mean arterial pressure. Furthermore, when the two populations were compared for the same level of blood pressure, using distensibility--and compliance--pressure curves, it was clear that isobaric distensibility and compliance of hypertensives were not significantly lower than those of normotensives, being either unchanged or higher. CONCLUSIONS: These findings are in contrast with the well-known decrease in compliance of proximal large arteries due to hypertension. Whether such a difference between proximal large arteries and distal medium-sized arteries may be related to the structural vascular changes observed with long-standing hypertension is still difficult to analyse in humans, and requires further investigation.

Cardiac and vascular structural changes in normotensive subjects with parental hypertension.

OBJECTIVE: To evaluate whether a predisposition to hypertension is associated with early cardiac and vascular alterations. SUBJECTS: Twenty-five normotensive subjects with both parents hypertensive (group 1) and 28 age- and sex-matched control subjects with both parents normotensive (group 2). METHODS: In the two groups the measurements included: clinic blood pressure; left ventricular end-diastolic diameter, septal wall thickness and posterior wall thickness (by echocardiography); minimal forearm and calf vascular resistances (i.e. resistance assessed immediately after prolonged ischaemia, which depends on arteriolar wall thickness); and baseline and postischaemic radial artery compliance-pressure curves over the systolodiastolic pressure range (by echotracking device and finger blood pressure). RESULTS: Group 1 had a slightly higher clinic blood pressure, and septal and posterior wall thickness, than group 2. Minimal forearm vascular resistance was clearly greater in group 1 than in group 2, whereas minimal calf vascular resistance was not significantly different in the two groups. Radial artery compliance was also similar in the two groups. CONCLUSIONS: Parental predisposition to hypertension is accompanied by cardiac and arteriolar structural changes qualitatively similar to those found in hypertensive patients, although arteriolar structural changes do not involve all vascular beds. Arterial compliance is not altered in this condition. Vascular changes may be determined by mechanisms other than blood pressure elevation.

Evaluation of the antihypertensive effect of celiprolol by ambulatory blood pressure monitoring.

The use of ambulatory blood pressure monitoring has gained popularity because it is not subject to those limitations associated with traditional sphygmomanometry (inaccuracy of blood pressure readings, low number of readings, and failure to represent daytime blood pressure readings). In the present study, we provide evidence that the 24-hour mean blood pressure obtained through intraarterial blood pressure measurements in ambulatory patients provides a more accurate diagnosis (and perhaps a prognosis) of hypertension than that provided by cuff-obtained casual blood pressure measurement. Furthermore, despite a reduction in the amount and in the accuracy of the information obtained, blood pressure data provided by noninvasive blood pressure monitoring are also more accurate diagnostically than cuff-obtained casual blood pressure measurements. In 15 essential hypertensive patients in whom celiprolol, 400 mg once daily, was compared with placebo in a randomized double-blind crossover study, the use of noninvasive 24-hour automatic blood pressure monitoring showed that in responsive patients, celiprolol induced a sustained reduction in systolic and diastolic blood pressure throughout the 24 hours. The blood pressure reduction was also apparent during the night, despite the concomitant occurrence of a slight tachycardia. These findings demonstrate that once-daily administration of celiprolol provides an effective lowering of the 24-hour blood pressure profile. This dosing schedule can therefore be regarded as appropriate for antihypertensive therapy.

Ambulatory blood pressure monitoring in the design of studies on antihypertensive drug efficacy.

Ambulatory blood pressure monitoring (ABPM) provides advantages for studies of the efficacy of antihypertensive drugs in addition to demonstrating antihypertensive effects in daily life conditions. For example, ABPM is devoid of the "white coat" effect and can thus more precisely estimate the relative proportion of responders and nonresponders to treatment. It also may reduce the study size because of the greater reproducibility of 24 h average blood pressure (BP) (as compared to clinic BP) and the lack of a substantial placebo effect, which eliminates the need for a placebo group. Some disadvantages exist, including the inability of automatic ABPM to consistently provide accurate BP readings and to estimate BP variability. Finally, hourly average BPs are less reproducible than their average 24 h counterpart, which may make it more difficult to statistically demonstrate an antihypertensive effect throughout the 24 h. Some of these disadvantages, however, may be reduced in the near future by new ABPM devices.

Clinical value of ambulatory blood pressure monitoring.

Although office blood pressure measurement may be predictive of cardiovascular complications, it still has several limitations: first, the accuracy of its predictions is limited; second, the stress reaction it causes may lead to an overestimation of the need for treatment and to an underestimation of the therapeutic response in some patients; and third, because of this 'white-coat' reaction and the wide variation in blood pressure over 24 h, office blood pressure can only be an approximate reflection of 24-h average blood pressure values both during and in the absence of treatment. The alternative method of ambulatory blood pressure monitoring may represent a valuable approach in the clinical management of hypertension. Values derived by this method are largely devoid of the consequences of the 'white-coat' reaction and are more closely correlated to the organ damage associated with hypertension than those derived from office blood pressure measurement. However, longitudinal studies are needed to demonstrate whether ambulatory blood pressure monitoring is truly prognostically superior to the traditional method, and to determine precisely which are the blood pressure values within the 24-h period on which to base the diagnosis of hypertension to assess more accurately the efficacy of antihypertensive treatment. However, there is the suggestion that optimal blood pressure control probably consists of an even reduction of both daytime and night-time values, and that the wide variations in blood pressure that occur throughout 24 h should probably also be reduced and maintained on a long-term basis.

Balanced 24-hour blood pressure control by angiotensin-converting enzyme inhibitors administered once daily.

Traditional sphygmomanometric measurements may inaccurately reflect the actual blood pressure level over a 24-h period. This is due to several factors which are known to affect cuff blood pressure readings, including the limited number of readings obtainable throughout the 24 h and the alerting reaction and pressor response induced in patients by the presence of the physician. Twenty-four-hour ambulatory blood pressure monitoring has been reported to be superior to isolated cuff blood pressure readings in the diagnostic evaluation of hypertension and in assessing the blood pressure response to treatment. It does not trigger any emotionally induced pressor reaction and is able to provide a dynamic evaluation of blood pressure profiles over 24 h. The latter feature is particularly important in assessing the ability of once-daily antihypertensive treatment to reduce and maintain blood pressure at an appropriate level throughout the 24-h period. Studies to date using ambulatory blood pressure monitoring techniques suggest that once-daily administration of certain ACE inhibitors is capable of providing this long-term control of blood pressure. The 24-h antihypertensive action exerted by once-daily administration of ACE inhibitors is characterized by balanced blood pressure control throughout the day and night, and treatment does not appear to alter the neural mechanisms responsible for cardiovascular homeostasis, as suggested by the fact that these drugs have been shown not to affect 24-h blood pressure and heart rate variability. Furthermore, during administration of ACE inhibitors the sensitivity of arterial baroreceptor control of circulation is unaltered or even enhanced. These observations emphasise the potential importance of long-acting ACE inhibitors in the control of arterial hypertension.

24-h ambulatory non-invasive blood pressure monitoring in the assessment of the antihypertensive action of celiprolol.

The well-known limitations of traditional sphygmomanometer blood pressure measurements have led to the development of a number of invasive and non-invasive 24-h blood pressure monitoring techniques which provide information on blood pressure in daily life. A non-invasive portable blood pressure monitor (IRC Spacelab S5300 monitor) was used to assess the antihypertensive action of celiprolol, 400 mg once daily, in a randomized, double-blind, crossover, placebo-controlled study. After a washout period of 7 days, 15 patients with mild or moderate essential hypertension were subjected to three 24-h blood pressure recordings: at the end of washout, and after 1 month of placebo and celiprolol treatment. In the 10 responsive patients, celiprolol reduced 24-h systolic blood pressure, diastolic blood pressure and heart rate by 6.8%, 8.1% and 2.7%, respectively, when compared with placebo. The reduction in blood pressure was also evident during the night and the antihypertensive action of celiprolol was maintained 24-h after administration. Celiprolol had no effect on 24-h blood pressure or heart rate variability and, therefore, did not produce any alteration in cardiovascular homeostasis. These results demonstrate that celiprolol is an effective once daily treatment for hypertension.

Radial artery compliance in essential hypertension: effects of antihypertensive therapy with lacidipine.

OBJECTIVE: To evaluate the effects of antihypertensive therapy with lacidipine on the increase in radial artery compliance observed in mild essential hypertensive patients. METHODS: The study was performed in eight mild to moderate essential hypertensive patients in whom clinic blood pressure, radial artery diameter and radial artery compliance were evaluated before and after 3 months' administration of lacidipine, at a single daily dose of 4 mg. Radial artery diameter and compliance were evaluated by means of a high precision echo-tracking device able to assess arterial compliance over the blood pressure oscillations that characterize the cardiac cycle. RESULTS: Lacidipine treatment caused a significant reduction in clinic systolic and diastolic blood pressure, while the heart rate was not modified by the drug. Radial artery diameter and compliance were both reduced by lacidipine over the entire systolodiastolic blood pressure range. CONCLUSIONS: Chronic administration of lacidipine seems to reverse the increase in compliance observed in essential hypertension at the radial artery level. We suggest that lacidipine treatment can reverse an increase in the smooth muscle component in the arterial wall induced by hypertension.

Variability in arterial diameter and compliance: compliance modulation reserve.

BACKGROUND: Some antihypertensive drugs are known to increase arterial compliance in hypertensives; how far compliance can be increased is unknown. DESIGN: We studied eight mildly hypertensive patients to determine how far radial artery compliance can be acutely increased, i.e. the extent of the compliance modulation reserve. METHODS: We evaluated radial artery compliance by a new technique, assessing it throughout the cardiac cycle before and after the intra-arterial infusion of a vasodilator agent (papaverine). RESULTS: Before papaverine, compliance decreased progressively through diastolic to systolic blood pressure values. This was the case also during the papaverine infusion. However, over the full systolo-diastolic pressure range, compliance was increased by about 40% with papaverine. CONCLUSIONS: In hypertensive subjects radial artery compliance can be markedly increased on a acute basis, indicating that those antihypertensive drugs that improve compliance have a considerable reserve to act upon.

Vascular effects of lacidipine: a review of animal and human data.

AIM: To compare the vascular effects of lacidipine with those of other calcium antagonists. METHODS: A review of published studies. RESULTS: Experimental studies have shown that for a similar fall in blood pressure, lacidipine increased cardiac contractility while verapamil decreased cardiac contractility. In the rat aorta, the dose of lacidipine required to reduce a calcium-induced contraction by 50% was lower than that of all other calcium antagonists tested except nisoldipine. In human studies, especially, there are inherent limitations in the techniques available to measure regional blood flows under physiological conditions, making it difficult to compare the effects of different antihypertensive drugs. A recent study showed that renal blood flow was increased by lacidipine without any reduction in renal function. As in animals, vital organ perfusion was either preserved or increased. Further, maximal coronary vasodilation was associated with lower coronary resistance values during lacidipine treatment compared with pretreatment values. Another lacidipine study showed increased brachial artery compliance, while a study on the radial artery showed that lacidipine increased the compliance of this artery also. CONCLUSIONS: Lacidipine has vascular selectivity. Although regional blood flows are difficult to measure, due to inherent limitations in the techniques available, the evidence suggests that lacidipine produces vasodilation in essential hypertensive subjects while maintaining or even increasing vital organ perfusion. This appears to be due to a regression of the structural changes that characterize hypertension.

Testing the accuracy of blood pressure monitoring devices in ambulatory conditions.

In recent years technological progress has improved the construction of ambulatory blood pressure monitoring devices. This has resulted in devices able to measure blood pressure continuously and non-invasively, and also in lighter, less noisy and more accurate intermittent blood pressure monitors. The accuracy of monitors, however, is still tested by taking blood pressure measurements at rest, and testing against intra-arterial blood pressure values, in true ambulatory conditions, is very seldom used. When evaluated by the latter approach, devices such as SpaceLabs 5300 and the Sandoz SPS 1558 recorders can be substantially inaccurate. Newer devices such as the SpaceLabs 90202 and 90207 are also somewhat inaccurate, particularly when diastolic blood pressure is considered. However, hour-to-hour changes in blood pressure obtained by the SpaceLabs 90202 and 90207 monitors are qualitatively and quantitatively similar to those obtained by invasive methods. This makes it possible to describe the 24-h blood pressure profile more accurately.