Different effects of in vivo ouabain and digoxin on renal artery function and blood pressure in the rat

To investigate vascular mechanisms in hypertension, we isolated renal arterial rings from rats with ouabain-dependent hypertension and studied their function. In rats infused with ouabain for 5 weeks, systolic and mean blood pressures (BP) were increased relative to controls. Contractions evoked by high KCI solutions were greater in rings from ouabain-infused rats whereas the threshold concentrations and EC₅₀S for KCI and the peak caffeine contractures were not different. KCI contractures were not affected by 5 μM prazosin. Phenylephrine contractures were increased marginally in ouabain-infused rats, while acetylcholine-induced relaxation was normal. In vitro superfusion of rings with 10 nM ouabain or digoxin did not affect the measured parameters. Plasma ouabain, BP, and all evoked responses were normal one week following interruption of the ouabain infusion. In a second study, BP increased in ouabain (15 μg/kg/day, n=23), but not digoxin (30 μg/kg/day, n=12), or vehicle-infused (n=16) rats. KCI contractures were greater in rings from ouabain-but decreased in rings from digoxin-infused rats, respectively and correlated with systolic and mean BP (r=0.69, n=30, p2+ storage and Ca²⁺ influx in response to in vivo ouabain may underlie the increase in renal vascular resistance and hypertension in this model. The opposite effects of ouabain and digoxin on the hemodynamic and vascular parameters in this study indicate that these agents have novel mechanisms of action in vivo that may not be mediated exclusively by sodium-potassium pumps.