Plasma digitalis-like substance and altered function of arterial Na+,K(+)-ATPase have both been linked with elevated blood pressure, but the influence of antihypertensive therapy on these factors remains unknown. Therefore, we treated spontaneously hypertensive rats and normotensive Wistar-Kyoto rats with the angiotensin-converting enzyme inhibitor quinapril for 10 weeks. The therapy markedly reduced blood pressure and plasma digoxin immunoreactivity, and it normalized the elevated plasma Na+:K+ ratio in the hypertensive animals. Relaxations of endothelium-denuded denervated arterial rings induced by return of potassium to the organ bath upon precontractions elicited by potassium-free solution were used to evaluate the function of vascular Na+,K(+)-ATPase. The rate of potassium relaxation was faster in quinapril-treated hypertensive rats and in both Wistar-Kyoto groups than in the hypertensive controls. Potassium relaxation was also effectively inhibited by the Na+,K(+)-ATPase inhibitor ouabain in all groups. In addition, arterial contractions to potassium chloride and relaxations to nitroprusside were examined. The contractions to lower concentrations of potassium chloride (20 mM) were enhanced in untreated hypertensive rats when compared with the other groups, although the maximal responses were corresponding in all groups. The time to reach base-line tension after washout of potassium chloride (125 mM) and the relaxations to nitroprusside did not differ in the study groups. In conclusion, the present results showed that long-term angiotensin-converting enzyme inhibition in parallel reduced plasma digoxin-like factor, enhanced arterial potassium relaxation (probably reflecting enhanced function of Na+,K(+)-ATPase) and normalized plasma Na+:K+ ratio in this type of genetic hypertension.