Spironolactone improves endothelial function in congestive heart failure patients on angiotensin converting enzyme inhibitors

JACC

March 19,2003

Infarction

(TIMI)

frame

count

( 23

patients with SCF

ABSTRACTS

(CTFC)

method.

male, 4 female,

8 female,

mean age 47.5i7.4)

Results-

The

(45.6*9.6

frames,

mean

with normal

CTFC

(CTFC,)

p
Reactive

Endothelial

function

coronary

significantly

was

hyperemia

%. p
was not signifacantly (16.8+1.1 % versus CTFC,

The

percent

different 17.lkl.l

was strongly

in 27

higher

in patients

was significantly

nitroglycerine-induced

with

SCF

related to percent

diameter increase in (3.48+0.10 % versus

(NTG-induced)

dilatation

of FMD (r=-0.29.

p
dilatation

in the 57 subjects

(r=-0.23.

and the CTFC was well correlated

p
analysis

showed

that

dysfunction.

T. Jadhav,

Glasgow

Naveed

Royal Infirmary,

Sanar, John R. Petrie, William Glasgow,

United

as cardiac

‘syndrome

x’ (CSX),

Methods.

We recruited

matched obtained. topically

56 women

fulfilling

acetyl choline

and sodium

of myocardial

ischaemia.

of their metabolic with controls

the criteria

parameters

for CSX along

We and

with 25 healthy

nitroprusside

and laser Doppler

imaging

Results. There were significant differences between the CSX and HC with regards to indices of insulin resistance (p
HDL-cholesterol

(p=O.O12),

C-reactive

protein

(p
body

mass

index

(BMI) (p
and circulating

vascular

markers

(van willebrand

for insulin.

However

the differences

tion for serum leptin. The differences ment

factor, tissue plasminogen

Discussion.

Subjects

were further

in MF remained

with CSX exhibited

features

attenuated

highly significant of the insulin

after correc-

even after adjust-

MF suggests

not only endothelial

resistance

dysfunction

but more generalised

suggesting

other factors play a critical role

George A. Mansoor.

function

Despite angiotensin

Mary Beth Barry, Manny

persists

in patients

converting

with congestive

Health

Katsetos,

Center,

Twenty

patients

on optlmal

increase Baseline

and sublingual

nitroglycerin

inhibition

heart failure

(ACEI),

(CHF).

Results:

Basal

blood

pressure,

CT,

endothelial

Aldosterone

dys-

inhibition

at baseline,

as

at 8 weeks

(p=O.OB). NTG dilation

Changes in FMD were not related to age, gender, or statin use. Conclusion:

Spironolactone

Improves

endothelial

ejection

: [Final

did not change

function

was unchanged

fraction,

85_+11

9.3 + 5.4

9.0 + 4.9”

16.2 i9.6

17.8 + 6.0

14.4i7.1

*p=o.o17;

“p=o.oB

i177-133

Jinsheng

Endothelial Function of Coronary Arteries Distal to a Radioactive Stent Li, Jesse Rios. Jianhua Research

Cui. Nicolas A. Chronos,

Institute,

Norcross,

artery endothelial

Keith A. Robinson,

American

GA

dysfunction

distal to implanted

stents in angio-

has been shown to persist for 6 mo; this may be due in part to the local tisto Stent implant with release of paracrine factors to the downstream

Radioactive

StentS alter the local tissue

reaction including

inhibition

of cellu-

vessels downstream

of stent implant.

Methods:

Segments

of pig coronary

arteries 2-cm

distal to radioactive Au-198 sterns (RAD; n=l2. 20 pCi) and non-radioactive Au-197 sterns (sham; n=9) were studied one month after stent implant. Endothelium-dependent and -independent

functions

were investigated

in an organ-chamber

apparatus.

Results:

Contractile responses to KCI and PGF,,were similar in both groups as well as to normal reference vessels. After incubation with L-NAME, contraction to PGF2, was significantly increased

in RAD (2.11+0.409

vs. 3.71*0.4Og;

2.75kO.429; NS). Dose-responses (A23187) and endothelium-independent in the two groups.

However,

PcO.01) but not in sham (1.88+0.4Og

to endothelium-dependent, (sodium nitroprusside)

maximal

dose relaxation

(O.lnM)

showed a strong trend to be higher than in non-radioactive 20.2+11 .l%; P=O.O63) in relation to normal reference segments shown).

This difference

was completely

abolished

was augmented

by the presence

radioactive stem upstream thase activity was blocked.

to substance

P in RAD

group (47.8*7.9% vs. (50.2tll.5%; results not

in the presence

tissue environment

in a manner

of the downstream

of a radioactive

also increased These findings

of NO synthase

stent just upstream.

block-

coronary sensitivity

The presence

of a

contraclile response to PGF*, when NO synsuggest that radioactive stents alter the local

that chronically

coronary

vs.

receptor-independent relaxations were similar

influences

the contractile

and relaxant

vasculature.

presence

diameter

-

over the

Ulrich Hinh Eberhard Schulz, Hanke Mollnau, Alexandra August, Manhias Oelze, Maria Wendt, Thomas Munzel, Hamburg,

hypertension

van Sandersleben, University Hospital

Michael Hamburg

Germany and coronary

artery disease

species. We sought to determine

ware further randomized

cebo. Endothelial ant acetylcholine.

at serine

are associated

with activation

of the

the effects of metoprolol

of endot-

on All-induced

(CTR) All (1 mg/kg/d.

to recieve either metoprolol

oxidant

7d). All-treated

(Meto, 100 mg/kg/d)

or pla-

function was studied by isometric tension studies using the vasorelaxSuperoxide production was assessed by lucigenin chemiluminescence staining.

NO was quantified

using electron

spin resonance

239. All-infusion

caused

marked

attenuation

of the acetylcholine-response.

Superoxide was increased in aortas from All-treated animals. NO-bioavailability and cGK-I activity were decreased. Metoprolol significantly improved the abnormalities caused by All-infusion. We conclude that in experimental hypertension metoprolol, in addition to its mere antihy pertensive effects, positively modulates the level of oxidatlve stress that accounts for cardiovascular

pathology.

Acetylcholme

(ED50)

LDCL

NO

pVASPNASP

CTR

-7.55 (LogM)

84

100%

100%

CTR+Meto

-7.55 (LogM)

67

91%

1 14%

All

-6.40 (LogM)

145

54%

37%

AII+Meto

-7.05 (LogM)

115

92%

92%

over time. of diabetes

as early as 4 weeks in CHF

patients on ACEI. This effect may be due to reversal of aldosterone impairment helial nitric oxide activity, and may contribute to its clinical benefit in CHF.

Effects of Metoprolol on Oxidant Stress Parameters and Nitric Oxide Eioavailability in Angiotensin II Induced Hypertension

1177-134

spectroscopy. Activity of the NO downstream target cGK-I was studied by determining the phosphorylation status (pVASPNASP) of the vasodilator stimulated protein (VASP)

4, and 8 weeks. The percent

heart rate, and body weight

(X)

(LDCL) and dihydroethldium

on endothelial

study period. Interobserver variability m FMD measurement showed a mean difference of 0.5 + 0.5% (r=0.97). Compared to baseline, FMD improved significantly at 4 weeks (p=O.O17) and persisted

NTG-DILATION

88+12

5.5 L 4.3

stress and the NO-pathway. Male wistar rats were treated with (All) or without

(age 64 + 11 years; ejection fraction

in brachial artery diameter with FMD or NTG was defined diameter]lBaseline diameter x 1 OO(%).

(kg)

FMD (%)

animals

enzyme

CHF therapy

(NTG)

15

BODY WEIGHT

oxygen

24 + 9%) were treated with spironolactone (25 mg po daily). Brachial artery diameter was measured with ultrasound before and after hyperemia - defined as flow-mediated dilation(FMD),

822

14

renin-angiotensin-system. For both diseases O-receptor-inhibitors are part of standard therapy. Angiotensin II (All) induces endothelial dysfunction and formation of reactive

Richaid

Farmington,

may ameliorate this dysfunction. We studied the effects of spironolactone function in stable CHF patients on optimal doses of ACEI. Methods:

6528

Eppendor,

Saucier. W. David Hager, University of Connecticut Creighton University Medical Center, Omaha, NE Background:

70+9

Arterial

Spironolactone Improves Endothelial Function in Congestive Heart Failure Patients on Angiotensin Converting Enzyme Inhibitors K. Abiose,

11

vascu-

muscle dysfunction which may be important in the aetiology of myocardial Adjusting for leptln and insulin did little to attenuate these differences in MF

Ademola

692

RATE (beats/min)

syndrome.

lar smooth ischaemia.

1177-132

1222

HEART

function

Attenuation of these differences after correction for leptin highlights the importance of adiposity and insulm resistance in CSX. Impairment of both endothelial-dependent and independent

8 WEEKS

ade using L-NAME. Conclusions: Endothelium-dependent receptor-mediated vasomotor sensitiwty but not endothelium-dependent non-receptor-mediated

activator, and cellular adhesion molecules) were also different between the 2 groups (p
117 + 11

lar proliferation and potentiation of local inflammation. To evaluate the effect of radioactive stern implant on distal vessel function. we studied vasomotor reactivity of coronary

controls (HC group). Fasting blood samples and clinical measurements were Forearm cutaneous microvascular function was assessed by iontophoresis of applied

125219

vasculature.

R. Ferrell, Stuart M. Cobbe.

have evidence

REACTIVITY

SYSTOLIC BP (mmHg)

Background:Coronary

Kingdom

sought to characterise women with CSX in terms peripheral microvascular function (MF) as compared

ARTERY

4 WEEKS

plasty patients sue reactions

Background. Angina1 chest pain despite angiographically normal coronary arteries in the context of a positive exercise test is a common problem. A proportion of this group, labelled

ON BRACHIAL

INITIAL VISIT

Cardiovascular

Women With Cardiac Syndrome X Exhibit Features of the Insulin Resistance Syndrome and Impaired Peripheral Microvascular Function

1177-131

Sachin

regression

of FMD only (r=-0.37, p
with endothelial

OF SPIRONOLACTONE

295A

in all sub-

jects. When the patients with SCF were excluded, CTFC, was still inversely related to percent FMD (r=-0.36, pcO.O5).The CTFC, was also inversely related to NTG-induced the CTFC, was inversely related to percent sions- These findings suggest that endothelial

EFFECTS

and Prevention

lower than that in the

between patients with SCF and subjects with NCF %. p=O.87). Simple regression analysis showed that

and inversely

TABLE:

(22 male,

flow (NCF).

NCF group ( 189+87 % vs. 310%176%, pcO.01). The flow-mediated SCF group was significantly smaller than that in the NCF group 9.1 l+O.lO

was studied

mean age 47.6+ 6.7) and in 30 subjects

- Vascular Disease, Hypertension,