Cardiomegaly and vasoactive hormones in rats with chronic myocardial infarction: long-term effects of chlorothiazide

1. The effects of prolonged chlorothiazide treatment of left ventricular failure on cardiac hypertrophy, circulating vasoactive hormones and exchangeable body sodium were examined in rats with chronic myocardial infarction induced by left coronary artery ligation. Chlorothiazide therapy commenced either immediately or 2 weeks after infarction. For 4 weeks, the rats were given either chlorothiazide (50 mg day-1 kg-1) in their drinking water or drinking water alone. 2. Cardiac weight increased in untreated rats with infarction in comparison with sham-operated controls, indicating the presence of chronic left ventricular dysfunction, although exchangeable body sodium, plasma renin activity, plasma vasopressin and plasma osmolality remained unchanged. 3. Chlorothiazide raised haematocrit and plasma renin activity equally in rats with and without infarction, although exchangeable body sodium, plasma vasopressin and plasma osmolality were not changed by the treatment. Plasma atrial natriuretic peptide was 2-fold higher in rats with infarction and this response was not affected by chlorothiazide treatment. Chlorothiazide therapy did not prevent or reverse cardiac hypertrophy. 4. Chronic diuretic therapy in this experimental model of heart failure did not reduce extracellular sodium, plasma vasopressin or the extent of ventricular hypertrophy, possibly because the condition was associated with activation of the renin-angiotensin system.