Immunization of Dahl SS/jr rats with an ouabain conjugate mitigates hypertension

Inhibition of the Na+/K(+)-ATPase by a circulating endogenous digitalis- or ouabain-like substance has been associated with the pathogenesis of several forms of clinical and experimental hypertension. Inbred salt-sensitive Dahl SS/jr rats were immunized with either urease or a ouabain-urease conjugate, then challenged with a high salt diet. The salt-induced increase in blood pressure in the ouabain-urease-immunized animals was significantly less than that of the urease-inoculated rats. Sera of the ouabain-urease immunized animals cross-reacted with ouabagenin, digoxigenin, digoxin, and digitoxin, but not with aldosterone, corticosterone, deoxycorticosterone (DOC), 18-hydroxy DOC, or 19-nor DOC. The fact that hypertension was not completely blocked by immunization supports ample evidence that the disease in these animals is multifactorial with several genes involved.