CARDIOPROTECTIVE PROPERTIES OF PROGESTINES: INFLUENCE OF DROSPIRENONE ON MYOCARD IN EXPERIMENTAL HEART FAILURE

Abstract

Aim. To assess the influence of synthetic progesterone — drospirenone, on remodeling of the left ventricle myocardium (LV) in ovariectomized (OE) female rats under circumstances of experimental heart failure (EHF).Material and methods. The study was done on 25 female Wistar rats, mass 260-300 g. Twenty animals (in 2 months after bilateral ovariectomy) underwent modeling of EHF by subcutaneous load of 0,1% mesaton solution for 14 days with following swimming to profound exhaustion. Four rats were removed on 14th day of EHF. Sixteen experimental animals with EHF were selected to 3 groups: 10 underwent 14 days subcutaneous load of drospirenon (Sigma-Aldrich, USA), dose 2 mg/kg (n=5) and 0,5 mg/kg (n=5), 6 were being loaded saline 0,2 mL daily. On 28th day the animals were removed from the experiment. With light microscopy method, immune cytochemistry, morphometry the LV myocardium was investigated.Results. In OE rodents on the 14th day of EHF there was clear and significant heteromorphism of contractile cardiomyocytes (CMC) with the signs of hypertrophy and dystrophy; increase of the volume density (VD) of stroma, reorganized extracellular matrix (EM), expression of metalloproteases-2,9 (MMP-2,9) and tissue inhibitor of metalloproteases-1 (TIMP-1), CMC with apoptosis. After remodeling of EHF at 28th day in myocardium there was further increase of CMC number with significantly changed morphology and tinctorial properties, degradation of EM components. In rats receiving 14 days drospirenon, regardless of dosage, there was regression of pathological changes, decrease of CMC hypertrophy grade, as the nuclei, decrease of CMC with the signs of apoptosis, and stabilized EM components.Conclusion. The cardioprotective properties of drospirenon are discussed, that even in minimal therapeutic concentrations facilitates structural and functional rehabilitation of myocardium under conditions of gonade hormones deficiency and EHF.

Keywords

• progesterone
• myocardium
• heart failure
• extracellular matrix
• aldosterone
• drospirenone