Abstract
Piroximone is a cardiotonic agent (phosphodiesterase inhibitor) proposed for the treatment of congestive heart failure. The drug causes adrenal medullary proliferative disease (AMPD) in rats after 1 year or more of treatment. In this study we investigated the effects on adrenal chromaffin cells prior to the development of obvious hyperplasia. Male rats were administered 0, 300, or 600 mg/kg/day of piroximone in the diet for three months.For morphometry studies, adrenals from 5 rats/group were fixed in 10% formalin and stained with hematoxylin and eosin (H&E). For differentiation of chromaffin cell types, left adrenals from 5 rats/group were fixed in 2% glutaraldehyde and 4% EM grade formaldehyde and stained with Gomori's methanamine silver and also (after pretreatment with 2.5% potassium dichromate in 1% sodium sulfate) with H&E as well as toluidine blue. For electron microscopy studies, adrenal medulla from 5 rats/group was fixed in 5% glutaraldehyde with post-fixation in 4% paraformaldehyde.
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