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Summary
A series of experiments was carried out to investigate the comparative diuretic and natriuretic effects of indapamide and frusemide in saline loaded dogs, and the effects of indapamide on urinary diluting and concentrating mechanisms. Comparative studies were also conducted on the acute haemodynamic effects of the two drugs in anaesthetized dogs and in conscious renal hypertensive dogs.
The results showed that indapamide is an effective natriuretic agent whose site of action appears to be localized at the proximal segment of the distal nephron. Indapamide (1 mg/kg i.v.) did not change blood pressure and cardiac output in anaesthetized dogs. However, it induced a decrease in blood pressure and a moderate decrease in cardiac output in chronic renal hypertensive dogs as a result of its natriuretic effects. In contrast, frusemide (1 mg/kg i.v.) induced an immediate effect on the haemodynamics in anaesthetized and conscious dogs, probably due to excessive volume depletion. Cardiac output, mean pulmonary artery pressure and left ventricular end diastolic pressures were decreased. In addition, splanchnic discharges were strongly increased and intravenous infusion of isotonic glucose antagonized this effect. The increase in sympathetic tone did not appear after section of both carotid sinus nerves and vagal nerves, indicating a reflex mediated effect. It is concluded, therefore, that although both indapamide and frusemide are effective antihypertensive agents in the renal hypertensive dog, their haemodynamic effects are very different.