Impaired Baroreflex Function and Arterial Compliance in Primary

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Journal of Human Hypertension (1999) 13, 29–36  1999 Stockton Press. All rights reserved 0950-9240/99 $12.00 http://www.stockton-press.co.uk/jhh ORIGINAL ARTICLE Impaired baroreﬂex function and arterial compliance in primary aldosteronism

F Veglio, P Molino, G Cat Genova, R Melchio, F Rabbia, T Grosso, G Martini and L Chiandussi Department of Medicine and Experimental Oncology, University of Turin, Italy

The purpose of this study was to evaluate if changes in mary aldosteronism patients in the supine position (P vascular properties were related to baroreflex function = 0.002 and P Ͻ 0.05 respectively). Aldosterone in patients with primary aldosteronism. Twenty-three plasma levels (R2 = 0.31, P = 0.01),age,systolicand patients with primary aldosteronism, 22 essential hyper- diastolic BP, high and low frequency components of tensive patients and 16 normal controls were studied. diastolic BP variability were independently related to Continuous finger blood pressure (BP) was recorded by compliance in primary aldosteronism. In conclusion Portapres device during supine rest and active stand primary aldosteronism is associated with an impaired up. Compliance was estimated from the time constant baroreflex function related in part to a reduced arterial of pressure decay during diastole. Baroreflex sensitivity compliance. Despite a reduction of BP values and was calculated by autoregressive cross-spectral analy- aldosterone levels, surgical or pharmacological treat- sis of systolic BP and interbeat interval. The result was ment did not significantly change compliance values. that baroreflex gain and compliance were lower in pri-

Keywords: baroreﬂex; compliance; primary aldosteronism

Introduction of arterial pressure decay during the diastolic portion of the arterial pressure wave. During the development and progression of hyper- The aim of the present study was to evaluate if tension, the vascular structural changes may have the arterial compliance was reduced in patients with substantial effects on baroreflex activity. In patients primary aldosteronism and if the impaired spon- with essential hypertension, a reduced compliance taneous baroreflex gain was related to a reduced of carotid artery is partially related to baroreflex dis- 1 arterial compliance, analysing finger arterial press- function. ure waves recorded non-invasively by the Port- Abnormal circulatory reflexes have also been apres device. reported in hypertensive patients with primary aldosteronism.2 Recently, using the spectral analysis of blood pressure (BP) and heart rate variability, we Materials and methods found an impaired spontaneous baroreflex control of Subjects the heart rate in such patients.3 Several studies have shown that a chronic mineralocorticoid excess leads We studied 23 hypertensive patients with primary ± to an increased collagen production inducing a peri- aldosteronism (PA: age 47.8 2.3 years, 12M/11F), 22 BP-matched essential hypertensives (EH: age 47.5 vascular fibrosis and heart remodelling in rats and ± humans.4–6 Hence these vascular changes could 2.3 years, 13M/9F) and 16 normal controls (N: age ± reduce arterial compliance and impair the barore- 45.7 2.3 years, 8M/8F). The diagnosis of primary aldosteronism was established by standard endo- flex sensitivity. 11 Spectral analysis of BP and heart rate variability crine tests. The differential diagnosis between has become a useful tool to assess the spontaneous aldosterone producing adenoma (APA) and idio- baroreflex gain by means of cross-spectrum analysis pathic aldosteronism (IHA) was performed by a 6- and calculation of the alpha index.7,8 (131-I)-iodo-methylnorcholesterol adrenal scan and Furthermore, various methods have been pro- adrenal computed tomography; when the TC scan posed to calculate the parameters of the Windkessel was negative or inconclusive adrenal vein sampling model (including total arterial compliance) from was performed. Six patients had adrenal adenoma analysis of the peripheral arterial pressure wave.9,10 and 17 bilateral adrenal hyperplasia. In the conventional time-domain approach, com- There was no evidence of renal injury or cardiac pliance values are estimated from the time constant failure in any patient. The study was performed at our Clinical Division after informed consent had been obtained and patients were asked not to take Correspondence: Dr Franco Veglio, Cattedra di Medicina Interna, any antihypertensive drugs or other medication and Ospedale S. Vito, Strada S. Vito 34, 10133 Torino, Italy to follow a diet with a normal sodium content for Received 7 August 1998; revised and accepted 20 September 1998 almost 4 weeks before the test. Participants were Baroreflex in primary aldosteronism F Veglio et al 30 asked to refrain from smoking, drinking coffee and taking sedatives for at least 24 h before test onset. Ten PA patients (7M/3F: two APA/eight IHA) were also studied after 1 year after the treatment: two patients were treated with surgical therapy while eight subjects received pharmacological therapy (high dose of spironolactone). Two males dis- continued spironolactone because of side effects (gynaecomastia, and reduction of libido); at the time of the study they were treated with Ca-antagonists and/or alpha-blockers.

Protocol Study was performed in a quiet room between 9 am and 1 pm. After 30 min of supine rest, continuous finger BP was recorded by Portapres Model-2 device (TNO, Amsterdam, NL) at 200 Hz sampling frequency in the supine position for 15 min. The same procedure was repeated during 15 min of active stand up. Portapres provides an indirect measurement of BP in a finger based on the arterial volume- clamp method of Penaz and the physiocal (physiological calibration) criteria for the full unloading of the arteries in a manner identical to Figure 1 Top: Finger blood pressure record in a normal subject. Finapres.12,13 The same finger was used both in the Bottom: Diastolic portion of the blood pressure curve, used to supine and upright position. calculate compliance values.

Data analysis Spectral analysis and baroreflex gain Data were then downloaded on a PC and analysed For each period (supine and upright), a sequence of by the Beatfast program (TNO) to identify systolic 400 to 600 data points (5–10 min) was analysed. The (SBP) and diastolic (DBP) blood pressure values and stationary point of BP and interbeat interval data interbeat intervals (IBI) for each cardiac cycle: after was checked by visual inspection. Mean values of digital low pass filtering at 17 Hz, SBP is stored as SBP, DBP, IBI were calculated. In the frequency the highest pressure level during the ejection. DBP domain, power spectral analysis of SBP, DBP and is arterial end diastolic pressure just before the next IBI was performed by the autoregressive method upstroke begins. IBI is the time difference between (Burg method) using custom software implemented two following systolic pressures. on MATLAB program, after linear interpolation of data at 1 Hz frequency (to obtain equispaced data) Windkessel parameters and demeaning. The order of the autoregressive model was 13 ± 2. Compliance (C) was estimated from the time con- The total power was then divided into low fre- stant (␶) of arterial pressure decay during diastole quency (0.025 − 0.14 Hz, LF) and high frequency (Figure 1): ␶ = R*C, where R are peripheral resist- (0.14 − 0.4 Hz, HF) components. Spectral compo- ances. This method requires the computation of car- nents of IBI variability were expressed in normalised diac output (CO) and peripheral resistances (R): CO units (by dividing the power of a given component was estimated from the algorithm proposed and by the total variance from which the direct current validated with invasive studies by Cohn et al14 as a component had been subtracted, and multiplying by multivariate function of ejection time, heart rate, 100). The baroreflex gain was computed as alpha body surface area and age: stroke volume =−6.6 + index, ie, the square root of the ratio of the powers (0.25 ET) − (0.62 HR) + (40.4 BSA) − 0.51 (Age), of IBI in the LF range to corresponding SBP spec- where ET is the ejection time in milliseconds, HR is tral components: heart rate in beats per minute and BSA is body sur- ␣ =√ face area in squared meters. Peripheral resistances LFIBI / LFSBP were then calculated as mean arterial pressure/CO. For each period (supine and upright), a sequence Hormonal measurements of 150 to 250 arterial pressure waves were analysed. An automatic procedure implemented on MATLAB At the end of the supine period and after 1 h of software provides the computation of compliance, upright position, blood samples (7 ml) were with- CO and R for each wave, excluding artifacts and drawn from the antecubital vein into K2-EDTA abnormal waveforms: a minimum of 100 valid tubes placed on ice. Plasma was immediately separ- waves was required for further evaluations. Mean ated and stored at −40°C until assayed. Plasma renin values of Windkessel parameters were calculated for activity was assayed by radioimmunoassay (RIA) each period. measuring the quantity of generated angiotensin I Baroreflex in primary aldosteronism F Veglio et al 31 (Incstar Corp, Stillwater, MN, USA). Plasma aldos- and EH patients at rest, compared to N controls (P terone was measured by RIA (Sorin, Saluggia, Italy). = 0.004). In the upright position PA patients showed Plasma adrenaline and noradrenaline levels were higher total peripheral resistances than the other assayed by high performance liquid chromatography two groups. This parameter increased significantly with an electrochemical detector. in PA and EH patients after tilt. CO did not differ between all groups at rest and during tilt, and it decreased significantly during tilt Statistical evaluation in PA and N subjects. Statistical evaluation was performed by the Statisti- Spectral components of BP and HR variability are cal Analysis System (SAS Institute Inc, Cary, NC, shown in Table 3. Low frequency component of SBP USA) using ANOVA or t-test for paired data where and DBP variability at rest was significantly higher appropriate. Pearson moment product correlation in PA and EH patients compared to N subjects. test was performed to analyse the strength of the LFNU component of IBI variability in EH patients relationship between two variables. was significantly lower compared to N subjects after Further, multiple regression analysis with step- tilt. In both positions PA and EH patients showed a wise procedure was performed to evaluate the rela- lower baroreflex gain compared to N subjects. tive contribution of independent variables related to A direct correlation was found between baroreflex compliance. A value of P Ͻ 0.05 was taken as the gain and compliance in the supine position (r = 0.31; level of statistical significance. Results are given as P = 0.04, Figure 3) and during standing (r = 0.38, P means ± s.e.m. = 0.01) when both EH and PA patients were considered. Results An inverse relationship was found between LF component of SBP variability and compliance (r =− Table 1 shows main clinical and biochemical para- 0.49, P = 0.02) and baroreflex gain (r =−0.43, P = meters of patients studied. Body mass index was 0.03) in PA patients. Moreover, an inverse relation- higher in PA and EH patients compared to N sub- ship was found between aldosterone plasma levels jects. Aldosterone was lower in EH than PA patients, and compliance values in PA patients (r =−0.55, P whereas plasma renin activity was higher in EH = 0.01 at rest, r =−0.39, P = 0.08 after tilt, Figure 4). compared to PA patients. In the same group, aldosterone was also related to Haemodynamic parameters are shown in Table 2. the LF component of SBP variability (r = 0.63, P = Systolic and diastolic BPs were significantly higher 0.005). in PA and EH compared to N at rest (P Ͻ 0.0001) Multiple regression analysis with stepwise pro- and during tilt. Also in orthostatic position PA cedure was performed to identify independent vari- showed DBP values higher than EH. Heart rate at ables related to compliance variability. The model rest did not differ between the three groups. included the variables shown in Table 4. During standing, heart rate increased significantly Aldosterone plasma levels, age, systolic and dia- in all groups (P Ͻ 0.05). Windkessel compliance stolic BP, high and low frequency components of were significantly lower in PA patients compared to DBP variability were independently related to com- N and EH at rest (P Ͻ 0.05) (Table 2, Figure 2). pliance in PA patients in the supine position. Total peripheral resistances were higher in PA After treatment PA patients showed significantly lower aldosterone levels and systolic and diastolic BP values in both positions (P Ͻ 0.01); also total Table 1 Main clinical and biochemical parameters peripheral resistances were reduced at rest and after tilt (Table 5). Primary Essential Normal aldosteronism hypertensives controls (n = 23) (n = 22) (n = 16) Discussion 2 Age (years) 47.8 ± 2.3 47.5 ± 2.3 45.7 ± 2.3 Since 1966 Biglieri et al found the absence of BMI (kg/m2) 25.8 ± 0.6* 26.7 ± 0.8* 23.0 ± 0.7 hypertensive overshoot after the Valsalva man- Serum K (mEq/L) 3.6 ± 0.3 4.1 ± 0.1 4.1 ± 0.2 oeuver and the abnormal responses to changes in Serum creatinine 79 ± 280± 271±2 posture in patients with primary aldosteronism, pro- ␮ ( mol/L) viding definite evidence of impairment of circulat- Aldosterone (pmol/L) supine 832 ± 83† 296 ± 27 — ory reflex activity in such patients. upright 1467 ± 113†‡ 684 ± 163‡ — Recently, we showed an impaired baroreflex sen- PRA (ng (AI/L*s)) sitivity in patients with primary aldosteronism supine 0.08 ± 0.02† 0.29 ± 0.01 — using power spectral analysis of BP and heart rate upright 0.16 ± 0.02† 0.63 ± 0.18 — 3 Noradrenaline (nmol/L) variability. In the present study, we found that this supine 1.05 ± 0.11 — — alteration is in part related to a reduced compliance upright 1.59 ± 0.3 — — of the arterial tree. It is known that the arterial com- Adrenaline (nmol/L) pliance reduction may be related to high BP levels ± supine 0.58 0.03 — — in essential hypertension,15–17 however, the step- upright 0.63 ± 0.06 — — wise multiple regression analysis of our data shows BMI: body mass index; PRA: plasma renin activity. an independent and direct role of plasma aldos- *P Ͻ0.01 vs normal controls; †P Ͻ0.01 vs essential hypertensives; terone in reducing arterial compliance in patients ‡P Ͻ0.05 vs rest. with primary aldosteronism. Moreover, even if Baroreflex in primary aldosteronism F Veglio et al 32 Table 2 Haemodynamical parameters

Primary aldosteronism Essential hypertensives Normal controls Tilt (n = 23) (n = 22) (n = 16)

Rest Tilt Rest Tilt Rest

Systolic BP (mm Hg) 161 ± 5*** 160 ± 5*** 150 ± 3*** 145 ± 6*** 105 ± 4 116 ± 4 Diastolic BP (mm Hg) 85 ± 3.8*** 95 ± 3.3***†‡ 79 ± 2*** 78 ± 2*** 52 ± 366± 3‡ Heart rate (beats/min) 65 ± 274± 2‡ 69 ± 177± 2‡ 68 ± 284± 3‡ Cardiac output (L/min) 6.00 ± 0.13 5.49 ± 0.13‡ 6.25 ± 0.20 5.80 ± 0.21 6.03 ± 0.11 5.23 ± 0.15‡ Total peripheral resistances 1400 ± 54** 1775 ± 78**†‡ 1261 ± 51** 1402 ± 75 1046 ± 67 1374 ± 129‡ (105*N*s/cm5) Total arterial compliance 1.24 ± 0.05* 1.31 ± 0.06 1.43 ± 0.09 1.40 ± 0.10 1.55 ± 0.08 1.45 ± 0.1 (ml/mm Hg)

*P Ͻ 0.05 vs normal controls; **P Ͻ 0.01 vs normal controls; ***P Ͻ 0.0001 vs normal controls; †P Ͻ 0.05 vs essential hypertensives; ‡P Ͻ 0.05 vs rest. BP: blood pressure.

peripheral resistance and normal cardiac output in primary aldosteronism patients as previously reported.18,19 Lage et al1 found that in essential hypertensives, a reduced distensibility of the carotid artery blunts in part the baroreceptor response to increases in BP. In our study, we found that arterial compliance explains about 10% of baroreflex gain variability, suggesting the presence of multiple factors influ- encing baroreflex gain in primary aldosteronism patients.20–22 In fact, several mechanisms could be proposed, including: (a) stimulation of cardiac volume receptors,23 (b) modulation of peripheral sen- sory baroreceptive neurons (ie, by alteration in ions balance), or (c), a defect in central mechanisms involved in the coupling of the afferent baroreceptor ± Figure 2 Bar graphs show mean arterial compliance s.e.m. in activity to the efferent sympathetic drive.24 the supine position (í) and during tilt (). *P Ͻ 0.05 vs normal controls. However, in addition to the above mentioned functional mechanisms, structural changes of the arterial wall are likely to be involved, but to date essential hypertensive patients present a decrease of there were no studies that evaluated this issue in arterial compliance compared to normal controls, primary aldosteronism patients. this reduction does not reach the statistical signifi- Munakata et al25 described increased baroreceptor cance, showing an additional role of the aldosterone sensitivity in primary aldosteronism patients com- increase in the reduction of arterial compliance. In pared to essential hypertensives, while no difference addition, we confirm the evidence of increased total was found with respect to normotensives. These dis-

Table 3 Spectral parameters of blood pressure and IBI variability

Primary aldosteronism Essential hypertensives Normal controls (n = 23) (n = 22) (n = 16)

Rest Tilt Rest Tilt Rest Tilt

Systolic BP LF (mm Hg2) 22.5 ± 4.6** 26.9 ± 2.8 18.1 ± 2.5** 34.2 ± 5.8† 5.1 ± 1.0 63 ± 28‡ HF (mm Hg2) 5.4 ± 2.2 6.5 ± 1.1 2.6 ± 0.4 4.7 ± 0.8‡ 1.1 ± 0.2 25 ± 17‡ Diastolic BP 7.8 ± 1.4** 9.1 ± 1.3 7.1 ± 0.9** 12.4 ± 1.8‡ 3.0 ± 0.4 13.9 ± 2.3‡ LF (mm Hg2) 2.4 ± 1.0 1.7 ± 0.4 0.8 ± 0.1 1.5 ± 0.3 0.6 ± 0.1 3.7 ± 1.1‡ HF (mmHg2) IBI LF (NU) 53 ± 563± 456± 358± 4* 61 ± 574± 4‡ HF (NU) 44 ± 436± 435± 331± 338± 525± 4‡ LF/HF 3.0 ± 1.2 2.8 ± 0.6 2.1 ± 0.2 2.9 ± 0.5 2.7 ± 0.6 5.5 ± 1.3‡ BRG: ␣-index (msec/m Hg) 8 ± 0.8** 6.0 ± 0.8*‡ 8.2 ± 0.6** 6.4 ± 0.8* 13.9 ± 1.5 10.6 ± 1.9‡

*P Ͻ 0.05 vs normal controls; **P Ͻ 0.01 vs normal controls; ‡P Ͻ 0.05 vs rest. LF: low frequencies; HF: high frequencies; IBI: interbeat interval; NU: normalised unit; BRG: baroreﬂex gain. Baroreﬂex in primary aldosteronism F Veglio et al 33

Figure 3 Linear relationship between baroreﬂex gain and arterial compliance in primary aldosteronism and essential hypertensive patients. (ȣ) essential hypertensive patients (n = 22); (v) primary aldosteronism patients (n = 23).

Figure 4 Linear relationship between plasma aldosterone and arterial compliance in primary aldosteronism patients (supine). cordant results could be due to several factors: first, young to elderly (12–74 years) and this could all patients considered in that study were affected explain the different values of baroreflex sensitivity; by aldosterone-producing adrenal adenoma; second, third, their normal controls showed lower baroreflex although the mean ages were similar in the two stud- gain compared to those obtained in most studies.26–28 ies for all groups, their patients ranged from very Since baroreflex sensitivity decreases with age, the Baroreflex in primary aldosteronism F Veglio et al 34 Table 4 Multiple regression analysis with a reduction in arterial compliance32:in humans, mineralocorticoids increase pressor Dependent: Compliance* responsiveness to noradrenaline and angiotensin II.33,34 In this study we confirm higher LF compo- 2 Partial R P nents of systolic and diastolic BP variability, related to sympathetic vasomotor regulation, in patients l Aldosterone 0.3 0.31 0.01 n Age 0.1 0.44 0.05 with primary aldosteronism compared with normal d Systolic BP 0.1 0.56 0.05 subjects. The LF component of SBP was indirectly e Diastolic BP 0.1 0.65 0.06 associated to compliance, to total peripheral resist- p LF-SBP NS ances and to baroreflex gain, suggesting that the e HF-SBP NS n LF-DBP 0.1 0.68 0.1 increased pressor responsiveness to sympathetic d HF-DBP 0.1 0.74 0.09 drive could also explain the higher stiffness of the e LF-IBI NS arterial tree and the reduced baroreflex gain. The n HF-IBI NS finding of normal plasma noradrenaline and adre- t LFHF NS naline levels confirms that sympathetic outflow is not modified, as previously reported.35,36 LF: low frequencies; HF: high frequencies; BP: blood pressure; IBI: interbeat interval; BRG: baroreflex gain; TPR: total peri- In our study, we used the cross-spectral analysis pheral resistances. of interbeat interval and BP variability to evaluate *Primary aldosteronism patients (n = 23); supine position. baroreflex sensitivity. This method offers several advantages on drug-induced baroreflex (eg, phenyl- presence of elderly subjects could explain these ephrine method), including the analysis of spon- lower values. Analogous methodological differences taneous fluctuations and the avoidance of drug 29 administration that could itself affect baroreflex sen- between another study of the same author and our 37,38 own could explain the discordant results about BP sitivity. variability in primary aldosteronism patients. BP variability was evaluated by beat-to-beat non- In normal subjects, Neutel et al30 found that invasive BP recorded by the Portapres device: this higher aldosterone plasma levels tended to be asso- method has been shown to provide reliable BP ciated with reduced proximal arterial compliance. values at rest and during laboratory manoeuvres. Moreover, a chronic mineralocorticoid excess leads Moreover it can be used to assess BP variability by to an increase in type I and III collagen mRNA, spectral analysis, with caution in the interpretation inducing a perivascular fibrosis and vascular of low frequency components of SBP because of remodelling in heart and vessels of human and ani- their magnification by non-invasive vs intra-arterial mal models.4–6 approach.39 However in this study, the same In vitro studies showed that aldosterone stimu- approach was used in each group. thus, it is unlikely lates collagen synthesis in cultured adult rat cardiac that the differences between groups were biased. fibroblasts, in concentrations similar to those found The assessment of arterial compliance of the in renovascular hypertension: this response appears Windkessel model was performed using the dia- to occur via type I corticoid receptor.31 As in essen- stolic pressure decay model method on non-invasive tial hypertension,1 the higher stiffness of the arterial BP recorded from a finger artery. Although the walls can be responsible for the reduced discharge actual contour of the diastolic waveform may differ of the baroreceptors in primary aldosteronism at different recording sites, these differences relate patients. primarily to varying initial conditions that do not Finally, ␣-adrenergic stimulation is associated influence the time constant of BP decay.10,14.

Table 5 Haemodynamical and biochemical parameters in primary aldosteronism before and after treatment

Primary aldosteronism Primary aldosteronism before treatment after treatment (n = 10) (n = 10)

Rest Tilt Rest Tilt

Systolic BP (mm Hg) 158.6 ± 6.2 151.1 ± 6.1 133.9 ± 6.1** 140.9 ± 5.9* Diastolic BP (mm Hg) 83.4 ± 5.9 91.3 ± 5.2 67.8 ± 4.4** 77.9 ± 3.7** Heart rate (beats/min) 66.4 ± 3.6 75.7 ± 4.2 68.0 ± 3.3 75.7 ± 4.2 Cardiac output (L/min) 6.1 ± 0.22 5.45 ± 0.20 6.34 ± 0.19 5.84 ± 0.18 Total peripheral 1423.3 ± 88.5 1669.5 ± 96.8 1147.9 ± 59.1* 1365.2 ± 71.0* resistances (105*N*s/cm5) Total arterial compliance 1.29 ± 0.09 1.30 ± 0.11 1.39 ± 0.10 1.29 ± 0.05 (ml/mm Hg) BRG: ␣-index 7.87 ± 1.1 4.94 ± 0.7 6.75 ± 1.64 7.22 ± 1.7 (msec/mm Hg) Aldosterone (pmol/L) 959.8 ± 125.1 1515.9 ± 189.4 441.0 ± 116.5* 740.6 ± 169.2** PRA (ng(AI/L*s) 0.09 ± 0.01 0.16 ± 0.04 0.27 ± 0.09 0.69 ± 0.35

*P Ͻ 0.05 vs pre-therapy; **P Ͻ 0.01 vs pre-therapy. BP: blood pressure; BRG: baroreflex gain; PRA: plasma renin activity. Baroreflex in primary aldosteronism F Veglio et al 35 Moreover finger BP recording provides a good esti- determining arterial compliance. J Hypertens 1992; 10: mate of intra-arterial pressure in individual sub- S11–S14. jects40 and we obtained haemodynamic data, 11 William FWJ, Klee GG. Primary aldosteronism. Diag- (averaging at least 100 consecutive waves) superim- nostic evaluation. Endocrinol Metab Clin North Am posable to those obtained in previous studies.18,19 1988; 17: 367–395. 12 Imholz BPM et al. Feasibility of ambulatory, continu- In conclusion the present study shows that the ous 24-hour finger arterial pressure recording. Hyper- impaired baroreflex sensitivity of primary aldos- tension 1993; 21: 65–73. teronism patients is also related to a reduced com- 13 Penaz J. Photoelectric measurement of blood pressure, pliance of the arterial tree. Plasma aldosterone levels volume and flow in the finger. Digest 10th Int Conf are associated to compliance changes. Two main Med Bio Engen, Dresden 1973, p 104. mechanisms that may be involved include an 14 Cohn JN et al. Noninvasive pulse wave analysis for the increased collagen deposition in the vessel walls early detection of vascular disease. Hypertension 1995; and/or an increased responsiveness to adrenergic 26: 503–508. stimulation. 15 Messerli FH, Frohlich ED, Ventura HO. Arterial com- Hence, our findings support the hypothesis that pliance in essential hypertension. J Cardiovasc Pharm- acol 1985; 7: S33–S35. aldosterone may be responsible for structural 16 Ventura H et al. Impaired systemic arterial compliance changes of the arterial tree. Treatment of primary in borderline hypertension. Am Heart J 1984; 108: aldosteronism in our patients do not significantly 132–136. modify compliance values, in spite of a reduction of 17 Simon A, Levenson J. Use of arterial compliance for BP, aldosterone and total peripheral resistances evaluation of hypertension. Am J Hypertens 1990; 3: mean levels. Thus, we may suppose that structural 97–105. modification of the arterial tree may take longer to 18 Williams ED et al. Body elemental composition, with resolve. It is also possible that the arterial changes particular reference to total and exchangeable sodium may be irreversible. On the other hand, the lack of and potassium and total chlorine, in untreated and change in arterial compliance after treatment may treated primary aldosteronism. J Hypertens 1984; 2: 171–176. reflect the use of medical therapy (spironolactone) 19 Wenting GJ, Man in’t Veld AJ, Derkx FHM, Schalek- in the majority of primary aldosteronism patients. amp MADH. Recurrence of hypertension in primary Even if the mean aldosterone level is reduced after aldosteronism after discontinuation of spironolactone. treatment, this is not true in each patient and it Time course of changes in cardiac output and body could be responsible for the lack of increase in fluid volumes. Clin Exp Hypertens [A] 1982; 4: arterial compliance. 1727–1748. Further studies are needed to evaluate if these 20 Wang W, McCain J, Zucker I. Aldosterone reduces alterations may play a remarkable role under a prog- baroreceptor discharge in the dog. Hypertension 1992; nostic and therapeutic point of view in primary 19: 270–276. aldosteronism patients. 21 Wang W. Chronic administration of aldosterone depress baroreceptor reflex function in the dog. Hyper- tension 1994; 24: 571–575. References 22 Butler GC, Senn BL, Floras JS. Influence of Atrial 1 Lage SG, Polak JF, O’Leary DH, Creager MA. Relation- Natriuretic Factor on spontaneous baroreflex sensi- ship of arterial compliance to baroreflex function in tivity for heart rate in humans. Hypertension 1995; 25: hypertensive patients. Am J Physiol 1993; 265: 1167–1171. H232–H237. 23 Veelken R et al. Impaired cardiovascular reflexes pre- 2 Biglieri EG, McIlroy MB. Abnormalities of renal func- cede deoxyorticosterone acetate-salt hypertension. tion and circulatory reflexes in primary aldosteronism. Hypertension 1994; 24: 564–570. Circulation 1966; 33: 78–86. 24 Chapleau MW et al. Structural versus functional 3 Veglio F et al. Spectral characteristics of heart rate and modulation of the arterial baroreflex. Hypertension blood pressure variability in primary aldosteronism. 1995; 26: 341–347. Am J Hypertens 1995; 8: 479–486. 25 Munakata M et al. Increased gain in baroreceptor-heart 4 Robert V et al. Increased cardiac types I and III col- rate reflex in patients with primary aldosteronism. lagen mRNAs in aldosterone-salt hypertension. Hyper- J Hypertens 1995; 13: 1648–1653. tension 1994; 24: 30–36. 26 Herpin D, Ragot S. Mid- and long-term reproducibility 5 Weber KT et al. Vascular remodelling and mineral- of noninvasive measurements of spontaneous arterial ocorticoids. J Endocrinol Invest 1995; 18: 533–539. baroreflex sensitivity in healthy volunteers. Am J Hyp- 6 Rizzoni D et al. Structural changes of small resistance ertens 1997; 10: 790–797. arteries in patients with secondary hypertension. Sev- 27 Watkins LL, Grossman P, Sherwood A. Noninvasive enth European Meeting on Hypertension, Milan, 1995; assessment of baroreflex control in borderline hyper- 159 (Abstract). tension. Hypertension 1996; 28: 238–243. 7 Robbe HWJ et al. Assessment of baroreceptor reflex 28 Castellano M et al. Relationship between sympathetic sensitivity by means of spectral analysis. Hypertension nervous system activity, baroreflex and cardiovascular 1987; 10: 538–543. effects after acute nitric oxyde synthesis inhibition in 8 Parati G, Saul JP, Di Rienzo M, Mancia G. Spectral humans. J Hypertens 1995; 13: 1153–1161. analysis of blood pressure and heart rate variability in 29 Munakata M et al. Decreased blood pressure varia- evaluating cardiovascular regulation. A critical bility at rest in patients with primary aldosteronism. appraisal. Hypertension 1995; 25: 1276–1286. Am J Hypertens 1998; 11: 828–838. 9 Shim Y et al. Arterial Windkessel parameter esti- 30 Neutel JM, Smith DHG, Graettinger WF, Weber MA. mation: a new time domain method. Ann Biomed Dependency of arterial compliance on circulating neu- Engineering 1994; 22: 66–77. roendocrine factors and metabolic factors in normal 10 Finkelstein SM, Cohn JN. First and third-order models subjects. Am J Cardiol 1992; 69: 1340–1344. Baroreflex in primary aldosteronism F Veglio et al 36 31 Brilla CG, Zhou G, Masubara L, Weber KT. Collagen 36 Miyajima E et al. Muscle sympathetic nerve activity in metabolism in cultured adult rat cardiac fibroblasts: renovascular hypertension and primary aldosteron- response to angiotensin II and aldosterone. J Mol Cell ism. Hypertension 1991; 17: 1057–1062. Cardiol 1994; 26: 809–820. 37 Parlow J et al. Spontaneous cardiac baroreflex in 32 Grassi G et al. Sympathetic modulation of radial artery humans. Comparison with drug induced responses. compliance in congestive heart failure. Hypertension Hypertension 1995; 25: 1058–1068. 1995; 26: 348–354. 38 Malliani A, Pagani M, Lombardi F, Cerutti S. Cardio- 33 Raab W, Humpreys RJ, Lepeschkin E. Potentiation of vascular neural regulation explored in the frequency pressor effects of norepinephrine and epinephrine in domain. Circulation 1991; 84: 482–492. man by desoxycorticosterone acetate. J Clin Invest 39 Omboni S et al. Spectral and sequence analysis of 1950; 29: 1397–1401. finger blood pressure variability. Comparison with 34 Friedman SM. Additive effects of aldosterone with analysis of intraarterial recordings. Hypertension 1993; vasopressin or angiotensin. Hypertension 1984; 6: 22: 26–33. 242–248. 40 Parati G et al. Comparison of finger and intra-arterial 35 Bravo E, Tarazi R, Dustan H, Fouad F. The sympathetic blood pressure monitoring at rest and during labora- nervous system and hypertension in primary aldos- tory testing. Hypertension 1989; 13: 647–655. teronism. Hypertension 1985; 7: 90–96.