Abstract
Eplerenone (EP), an aldosterone antagonist, is reported to produce renal and cardiac protective effects in noncanine species. However, there are no detailed reports available on cardiovascular effects of EP in dogs. This study aimed to determine effect of EP on echocardiographic parameters, blood pressures, and biochemical variables in healthy dogs. Five healthy Beagle dogs were randomly divided and repeatedly used in each of 3 dose groups, receiving 2.5, 5, or 10 mg/kg BW EP orally q24 h for 4 wks. Serum biochemical test, blood pressure, and Doppler echocardiography measurements were performed before EP administration and at 1, 2, and 4 weeks after EP administration. Treatment with EP reduced mean blood pressure in a dose-dependent manner and significantly (but in a dose-independent manner) decreased left atrium/aorta ratio, early diastolic transmitral flow, early diastolic transmitral flow/late diastolic transmitral flow, peak velocity of early diastolic transmitral flow/peak velocity of early diastolic mitral annular motion, left ventricle and right ventricle Tei indices, stroke volume, cardiac output, and mid systole myocardial velocity gradient 1 to 4 weeks after administration. Deceleration time of early diastolic transmitral flow significantly increased after EP administration. No significant changes were observed in serum biochemical variables. The results indicated that EP might reduce preload, thereby decreasing left atrial size. In addition, reduction of left ventricular stiffness may have theoretically taken place but this could not be tested using the present study design. It is suggested that EP administration within the dose range used in this study is safe for administration to healthy dogs. Further studies are needed to explore both safety and efficacy, as well as to seek a recommended dose range of EP treatment in client-owned dogs with heart disease.
Highlights
Aldosterone is a steroid hormone that is synthesized in the adrenal cortex and has a role in the renin-angiotensin–aldosterone system (RAAS)
Adult, neutered, female Beagle dogs were used in this study. e dogs were fed a standard commercial dry food formulated for dogs and were raised in an appropriate animal management facility. e physical and hematological examinations performed before the experiments confirmed that all dogs were healthy. e study protocol was principally based on the Guide for the Care and Use of Laboratory Animals developed by the Institute of Laboratory Animal Research of the National Research Council of Japan and approved by the Animal Research Committee of Tottori University
No significant changes were observed in Heart rate (HR) after EP administration within or between the groups (Figure 1(a))
Summary
Aldosterone is a steroid hormone that is synthesized in the adrenal cortex and has a role in the renin-angiotensin–aldosterone system (RAAS). It induces fluid retention via the renal mineralocorticoid receptor by reabsorbing sodium and water ions. In human medicine, aldosterone contributes to the development of congestive heart failure and cardiovascular disease (i.e., injury of the vascular endothelium and baroreceptor dysfunction) [2, 3]. Mineralocorticoid receptors are activated in human heart failure [5, 6], and their activation is involved in organ injury in rats, even with low concentrations of aldosterone in the blood [7]. Mineralocorticoid receptors are activated in human heart failure [5, 6], and their activation is involved in organ injury in rats, even with low concentrations of aldosterone in the blood [7]. erefore, it may be important to prevent both the adverse effects of aldosterone and the activation of the mineralocorticoid receptors for the improvement of heart failure
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