Effects of canrenone on blood pressure in rats with reduced renal mass

Canrenone, a metabolic product of spironolactone, which competes with ouabain for binding to Na-K-ATPase at the digitalis receptor site and by itself inhibits Na-K-ATPase, was administered intramuscularly to reduced renal mass-saline drinking hypertensive and reduced renal mass-distilled water drinking normotensive rats for 8 days. Reduced renal mass-saline hypertension in the rat, is a low renin, volume expanded form of hypertension. Rats with this type of hypertension have been shown to have depressed arterial Na-K pump activity and increased Na-K pump inhibitory activity in their plasma. Canrenone treatment caused a progressive decrease in blood pressure in the hypertensive rats and this was associated with normalization of Na-K pump activity in arteries. Water and salt intake and excretion did not change. On the other hand, canrenone progressively increased blood pressure in the normotensive rats and this was associated with positive inotropy in isolated papillary muscles. These findings suggest that the depressed pump activity and the pump inhibitor play a role in reduced renal mass-saline hypertension in the rat and that the rise in blood pressure in the normotensive rats probably reflects canrenone's ability, by itself, to inhibit Na-K-ATPase.