Aldosterone induces a vascular inflammatory phenotype in
the rat heart. Am J Physiol Heart Circ Physiol 283:
H1802–H1810, 2002. First published June 27, 2002; 10.1152/
ajpheart.01096.2001.—Vascular inflammation was examined
as a potential mechanism of aldosterone-mediated myocardial
injury in uninephrectomized rats receiving 1% NaCl-
0.3% KCl to drink for 1, 2, or 4 wk and 1) vehicle, 2)
aldosterone infusion (0.75 g/h), or 3) aldosterone infusion
(0.75 g/h) plus the selective aldosterone blocker eplerenone
(100 mgkg1 day1). Aldosterone induced severe hypertension
at 4 wk [systolic blood pressure (SBP), 210 3 mmHg
vs. vehicle, 131 2 mmHg, P 0.001], which was partially
attenuated by eplerenone (SBP, 180 7 mmHg; P 0.001
vs. aldosterone alone and vehicle). No significant increases in
myocardial interstitial collagen fraction or hydroxyproline
concentration were detected throughout the study. However,
histopathological analysis of the heart revealed severe coronary
inflammatory lesions, which were characterized by
monocyte/macrophage infiltration and resulted in focal ischemic
and necrotic changes. The histological evidence of coronary
lesions was preceded by and associated with the elevation
of cyclooxygenase-2 (up to 4-fold), macrophage
chemoattractant protein-1 (up to 4-fold), and osteopontin
(up to 13-fold) mRNA expression. Eplerenone attenuated
proinflammatory molecule expression in the rat heart and
subsequent vascular and myocardial damage. Thus aldosterone
and salt treatment in uninephrectomized rats led to
severe hypertension and the development of a vascular in-
flammatory phenotype in the heart, which may represent one
mechanism by which aldosterone contributes to myocardial disease
(RALES) demonstrated that spironolactone significantly improves outcomes in patients with severe heart failure. Use of angiotensin-converting–enzyme (ACE) inhibitors are also indicated in this same patient group. However,life-threatening hyperkalemia can occur when these drugs are used together.
methods
Juurlink and colleagues performed A population-based time-series analysis to examine trends in the rate of spironolactone prescriptions and the rate of hospitalization for hyperkalemia in ambulatory patients before and after the publication of RALES. They linked prescription claims data and hospital-admission records for more than 1.3 million adults 66 years of age or older in Ontario, Canada, for the period from 1994 through 2001.
Results: After the publication of rales there was 500% increase in spironolactone prescriptions with a 275% increase in hospitalizations, and 285% increase in deaths due to hyperkalemia
conclusions
The publication of RALES was associated with abrupt increases in the rate of prescriptions for spironolactone and in hyperkalemia-associated morbidity and mortality. Closer laboratory monitoring and more judicious use of spironolactone may reduce the occurrence of this complication
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