CHRONIC BLOOD-PRESSURE EFFECTS OF BUFALIN, A SODIUM-POTASSIUM ATPASE INHIBITOR, IN RATS

Endogenous Na+,K+-ATPase inhibitors may have a role in the mechanism of low-renin hypertension. Two such compounds have been characterized: ouabain from human plasma and resibufogenin from toad plasma. Previously, we examined the acute effects of ouabain and bufalin (which has the same structure as resibufogenin except for one H+) in normal rats. Bufalin raised blood pressure, but ouabain had little effect. In contrast, given chronically, ouabain substantially increased brood pressure in normal rats and 70% reduced renal mass rats on a salt-free diet. We have now examined the chronic effects of bufalin in rats. Normal rats received 14.8 mu g/kg per day bufalin or an equimolar dose of ouabain intraperitoneally for 6 weeks; 70% reduced renal mass rats also received 14.8 mu g/kg per day bufalin. Another group of normal rats received 29.6 mu g/kg per day bufalin intraperitoneally for 6 weeks. Respective control animals received vehicle. In contrast to ouabain, blood pressure did not increase in normal rats receiving the 14.8 mu g dose of bufalin. However, normal rats receiving 29.6 mu g bufalin and 70% reduced renal mass rats receiving 14.8 pg bufalin developed significant increases in blood pressure. Increases in blood pressure were associated with decreases in myocardial Na+,K+-ATPase activity and correlated with increased plasma Na+,K+-ATPase inhibitory activity. Thus, although bufalin is a more potent presser agent than ouabain when both agents are given acutely, ouabain is at least as potent a vasopressor agent as bufalin when given chronically. Thus, both are presser agents, more so in the presence of reduced renal mass, when given chronically in the rat.