The antagonism of aldosterone receptor prevents the development of hypertensive heart failure induced by chronic inhibition of nitric oxide synthesis in rats

Autor: Yoshihiro Asano, Akio Hirata, Hitonobu Tomoike, Yasunori Shintani, Seiji Takashima, Shoji Sanada, Satoru Yamasaki, Masafumi Kitakaze, Tetsuo Minamino, Osamu Tsukamoto, Ken-ichiro Okada, Masatsugu Hori, Masashi Fujita, Liao Yulin
Rok vydání: 2006
Předmět:
Male
Spironolactone
Rats
Inbred WKY
chemistry.chemical_compound
Random Allocation
Mineralocorticoid receptor
Transforming Growth Factor beta
Pharmacology (medical)
Aldosterone
Mineralocorticoid Receptor Antagonists
Aldosterone Receptor Antagonist
NF-kappa B
General Medicine
Immunohistochemistry
Eplerenone
NG-Nitroarginine Methyl Ester
Hypertension
Drug Therapy
Combination
Cardiology and Cardiovascular Medicine
medicine.drug
medicine.medical_specialty
Heart Ventricles
Blotting
Western
Nitric Oxide
Nitric oxide
Transforming Growth Factor beta1
Internal medicine
Proliferating Cell Nuclear Antigen
medicine
Animals
Cytochrome P-450 CYP11B2
RNA
Messenger
Protein Precursors
Pharmacology
Heart Failure
business.industry
medicine.disease
Fibrosis
Actins
Peptide Fragments
Rats
Preload
Endocrinology
Blood pressure
Receptors
Mineralocorticoid
chemistry
Heart failure
business
Zdroj: Cardiovascular drugs and therapy. 20(2)
ISSN: 0920-3206
Popis: Aldosterone promotes cardiovascular inflammation and remodeling, both of which are characteristic changes in hypertensive and failing hearts. Since chronic inhibition of nitric oxide (NO) synthase with N(omega)-nitro-L-arginine methyl ester (L-NAME) induces systemic hypertension associated with cardiovascular inflammation and remodeling, we examined the potential role of aldosterone in this process using eplerenone, a selective aldosterone receptor antagonist. Ten-week-old male Wistar-Kyoto rats were randomly divided into 3 groups: the control group (no treatment), the L-NAME group (received L-NAME 1 g/L in drinking water), and the L-NAME+Eplerenone group (L-NAME plus eplerenone at 100 mg/kg/day). After 8 weeks of the treatment, the L-NAME group showed significantly higher systolic blood pressure than the control group (198 +/- 7 vs. 141 +/- 3 mmHg, P0.05). Eplerenone did not affect the increase in blood pressure caused by L-NAME (189 +/- 12 mmHg). Chronic inhibition of NO synthesis increased the plasma aldosterone concentration and CYP11B2 mRNA in adrenal glands. Cardiac inflammation and fibrosis were detected in the L-NAME group, while both changes were completely prevented by eplerenone. Cardiac hypertrophy was induced in L-NAME group, but was partially prevented by eplerenone. In the L-NAME group, left ventricular fractional shortening (LVFS: 27 +/- 2 vs. 38 +/- 1%) and E/A ratio (1.7 +/- 0.1 vs. 2.1 +/- 0.1) were significantly lower and LV end-diastolic pressure (LVEDP) was higher (4.9 +/- 0.6 vs. 13.9 +/- 0.5 mmHg) without LV enlargement, compared with those in the control group (P0.05). Eplerenone completely normalized LVFS (36 +/- 2%), E/A ratio (2.2 +/- 0.1), and LVEDP (6.2 +/- 0.7 mmHg). These results suggest that chronic inhibition of NO synthesis induces cardiac inflammation and dysfunction via an aldosterone receptor-dependent mechanism.
Databáze: OpenAIRE
Externí odkaz: