Interactions Between Aldosterone, Spironolactone and the Cardiotonic Steroids
Abstract (Summary)We have reported that rats subjected to partial nephrectomy (PNx) or administration of marinobufagenin (MBG) developed an increase in blood pressure, heart size, diastolic dysfunction, and cardiac fibrosis. Spironolactone (S) has been demonstrated to attenuate cardiac fibrosis in both experimental animals and humans with heart failure. We investigated the effects of treatment of S in the cardiomyopathy. Rats were divided into four groups: one group PNx and a second group sham surgery (C), placement of a minipump of S in another group and PNx + S in the final group. Rats were studied at 4 wk. PNx rats had higher systolic blood pressure, cardiac fibrosis than C. S did not differ significantly from C. PNx +. S had substantially attenuated cardiac growth and fibrosis and decreased blood pressure (all p<0.01). These data suggest that S antagonizes MBG induced signaling which leads to cardiac fibrosis in the PNx model and raises the tantalizing question whether this mechanism explains at least part of the clinical beneficial effects of S on cardiac fibrosis in this and other settings.
School Location:USA - Ohio
Source Type:Master's Thesis
Date of Publication:01/01/2008