Peripheral action of spironolactone: Improvement in arterial elasticity

Peripheral Action of Spironolactone: Improvement in Arterial Elasticity Gilbert Lagrue, MD, Jean-Claude Ansquer, MD, and Andre Meyer-Heine, MD

Arterial elasticity, whiih can be assessed by means of a piezogram, is thought to be involved in the development of by-. In hypertensive patients (and with aging in normal subjects), arterial elasticity is redu+. Long-term administration of spironolactone, fi blockers, or a /3=blocker/dihydralazine combination to hypertensive patients sufficiently reduced systolic and diastolic blood preswre to about the same extent; however, only spironolactone had any effect on piexoelectric indexes of arterial elasticity. (Am J Cardiol19SO#S:SK-1lK)

I

n recent years, an increasingly important role has been attributed to arterial elasticity in the development of hypertension. Arterial elasticity (or distensibility) can be assessed by the velocity of the pressure wave along the arterial wall, which increases as elasticity decreases. This velocity can be calculated directly by measuring the amount of time for the wave to travel (transmission) between 2 points in the arterial system, e.g., from the carotid artery to the pedal artery or the carotid artery to the radial artery. This velocity is increased in hypertensive subjects, and it gradually increases with age, as a sign of arterial aging (Fig. 1, Table I).‘-5 MEASURING

From the Department of Nephrology, HBpital Henri Mondor, Creteil, France. Address for reprints: Gilbert Lagrue, MD, Hbpital Henri Mondor, Boulevard de Lattre de Tassigny, 94010 Criteil, France.

ARTERIAL

ELASTICITY

The carotid piezogram records waveforms of (arterial) blood pressure obtained noninvasively by means of a piezoelectric pressure gauge that translates pressure variations into variations of electric potential. The curve is recorded on an oscilloscope, with a spot sectioned at l/lOOth of a second. The waveform is the result of the intersection of 2 fundamental waves: the primary wave of ventricular pressure and a reflection wave (dicrotic wave). The peak of the curve corresponds to the systolic blood pressure and the trough corresponds to the diastolic blood pressure (Fig. 2). Also, the curve is characterized by various factors that regulate blood pressure, especially cardiac output (ventricular pressure) and peripheral resistance, of which arterial elasticity is a component.3*4 Velocity can also be determined indirectly by measuring the duration of the crest of the dicrotic wave, which is closely correlated with the transmission time (r = 0.75; p 1 year) were compared. The decreases in systolic and diastolic blood pressure were similar for the 3 treatment groups (Table IV), although it was more marked with spironolactone and the @blocker/dihydralazine combination than with /3 blockers alone. THE AMERICAN

JOURNAL

OF CARDIOLOGY

JUNE 19, 1990

SK

A SYMPOSIUM:

ROLE

OF ADLOSTERONE

AND

ALDOSTERONE

ANTAGONISM

IN CARDlOVASCULAR

Before

AU = sy&lgelder hyperlendve &te& presswe; DW = dkretk wave.

After S 12vr/lOO ma/d) BP = 140/80 mm Hg DW=100ms AB = 90 ms

S

BP = 200/I 20 mm Hg DW=40ms AB=40ms

Age: 40 years BP: 18OlllO mm Hg DW: 30ms

Age: 30 years BP: 130180 mm Hg DW: 140 ms

BP = blood

treatmmtandafter2yearsottreatmentwithspironolactone(s). Abbreviations as in Figure TABLE Age

Primary wave

lk

Reflection wave

I Changes

in Piezogram

1. Parameters

Transmission

Pressure Wave

Time

Velocity

<20 20-29 30-49 50-69 >70

210 170 154-162 130 110

TABLE (Carotid

II Age-induced Piezogram)

(ms)

DBP

>12

Changes

in Crest

of a healthy bleed

young

adult.

Ill

AB =

pressure.

However, the piezogram values were very different. With spironolactone, the dicrotic wave was significantly lengthened, indicating an improvement in arterial elasticity. This improvement was confirmed by an increase in the systolic slope. These changes were not found with either the p blockers (dicrotic wave moderately shortened) or with the &blocker/dihydralazine combination (dicrotic wave and systolic slope unchanged) (Fig. 3 and 4, Table IV). 1

of Dicrotic

W

Crest Wave

15-29 30-49 >50

137 f 41 87 f 21 50*29

Demographic

Parameters

Spironolactone group, 100-200 Mean age Men/women Mean duration of treatment Duration of hypertension Serum creatinine P-blocker group (n = 35) Mean age P-blocker + dihydralazine group Mean age Chronic hypertension

- Cardiac cycle-

~~rlopa;DBP=db~cMood~;II’=duraionot dii wave; SBP = systdll

TABLE Groups

(ms)

6.5 8 8.6-8.8 9.9-10.2

Age

I-

with Increasing

Age (Ye

Dicrotic wave

flGURE 2. Carotid piengram

MEDICINE

mg/day

Wave

of Dicrotic (ms)

of the Three

Patient

(n = 33) 46 years (21-64) 23/10 44 months (6-72) 6.5 years (1-18) 9-13 mg/liter 38 years

(16-56)

46 years >150/90

(3061) (at rest)

(n = 19)

EiiOrnmHg

%:3JHg

1

CONCLUSIONS

It is clear, therefore, that these different agents reduce blood pressure by different mechanisms. As seen here, spironolactone improves arterial elasticity, possibly by changing reactivity to pressor substances, which are 1OK

THE AMERICAN

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65

FlGURE

bea-

4. Carotid

Abbrevlatlens

d

ah

piezogram

ot a hypertensive

1 year d tFeat-

as in Figure

1.

patient

~e a b wer

bedare

(~.m.

TABLE Carotid

IV Effect of Long-Term Administration Piezogram Indexes of Arterial Elasticity

Spironolactone Before After p blocker Before After p blocker + dihydralazine Before After

of Spironolaotone. 0 Blockers, or p Blocker (Dicrotic Wave and Systolic Slope)

+ Dihydralazine

on Blood

Pressure

Systolic BP

Diastolic BP

Dicrotic Wave (ms)

AB Duration (ms)

178 f 28 140 f 150

lDof15 8Of8*

41.2 f 29.6 54.2 f 34+

44f 15 60 f 16*

164f 21 149*23+

96i12 87 4~ 14+

61f34 51 f34

54f 57*

171 f 20 144 f 20+

97f 82f

51 f27 51 f 19

54f22 53& 18

15 11’

and

1 19

* p
known to dav an imwrtant role in vascular distensibility. This favoiabie vascilar effect could also be due to alteration of transmembrane sodium transport found with spirtinolactone. REFERENCES 1. Kannel WB, Wolf PA, McGee DL, Dawbert T, McNamara Systolic blood pressure, arterial rigidity and risk of stroke. JAMA 1229.

P, Castelli WP. 1981;245:1224-

2. Lax M, F&berg A, Cohen B. Studies of the arterial pulse wave. The normal pulse wave and itsmodification in the presence of a&al arteriosclerosis. J Chronic

Dis 1956;3:618-631.

3. Merillon JP. Lebras Y. Chastre J. Goureon G. Ondes incident= and r&fl&chies dans le systbmearttriel; application i l’inte;pr&ation quantitative de la morphologie de la pression aortique. Arch Maa[ Coeur 1983;76:120-127. 4. Meyer-Heine A, Ansquer J-C, Kazandjian M, Lagrue G. De I’analyse du carotidogramme au m&canisme de I’hvoertension arterielle. Sem H&I Paris _. 1987~53.~663-2669.

5. Simon AC, Levenson JA, Bouthier JD, Safar ME. Evidence of early degenerative changes in large arteries in human essential hypertension. Hyperfension

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