The Effects of Spironolactone Monotherapy on Blood Pressure and Myocardial Remodeling in Spontaneously Hypertensive Rats: A Stereological Study

Abstract

The aim of this study was to evaluate the cardiac structure of spontaneously hypertensive rats (SHRs) treated with different doses of spironolactone. Twenty SHRs were separated into four groups and treated for 13 weeks, as follows: one control group and three spironolactone treatment groups receiving doses of 5, 10 or 30 mg/kg/day. The spironolactone treatment either attenuated or prevented the tendency for increased blood pressure. However, the myocardial structure was not significantly affected by the spironolactone monotherapy treatment (all doses); it showed hypertrophied cardiac myocytes, focal areas of reactive fibrosis, inflammatory infiltrate and a decrease in the density of intramyocardial microvessels. None of the cardiac myocyte stereological parameters in the left ventricular myocardium showed significant differences among the SHR groups. The cardiac myocyte volume density was around 80%, the cardiac myocyte surface density varied from 3.6 to 4.1 × 10⁴ mm²/mm³ and the cardiac myocyte mean cross-sectional area varied from 351 to 415 µm². The connective tissue volume density of the SHRs treated with the highest dose of spironolactone was 75% lower than in the control SHRs, and this was the only significant difference found for this parameter among SHR groups. The intramyocardial vessels showed some differences when the control SHRs and the other SHRs were compared. The lowest intramyocardial vessel volume density was found in the control group (more than 20% lower than that in the treated SHRs), but no significant difference was detected among the treated SHRs (all doses). The intramyocardial vessel length density (Lv[v]) and surface density (Sv[v]) showed a similar tendency, being significantly greater in the treated SHRs than in the control rats. The Lv[v] was 45% greater in the high-dose spironolactone group than in the control group, and it was 28% greater in the high-dose spironolactone SHRs than in the other treated SHRs. The Sv[v] was 50% greater in the high-dose spironolactone SHRs than in both control and low-dose spironolactone SHRs. Long-term spironolactone monotherapy showed a partial effect in the preservation of intramyocardial vessels and also in the attenuation of interstitial fibrosis.