Previous studies show that endogenous ouabain, a cardiac digitalis‐like compound, may play a role in development of elevated pressure. The current study investigated the effect of acute intravenous (i.v.) ouabain on mean arterial blood pressure (MAP) in (mRen2)27 and mRen2.Lewis rats models of hypertension. Non‐invasive blood pressure recordings verified elevated systolic pressure in conscious rats. Under urethane/chloralose anesthesia, MAP was normalized in (mRen2)27 and mRen2.Lewis rats (101 ± 6 mmHg and 84.6 ± 6 mmHg). I.V. ouabain (40 μg/kg/bwt) increased MAP to 25% above baseline in (mRen2)27 and 45% in mRen2.Lewis rats, returning to baseline within 30 minutes. The effect of ouabain on baroreceptor reflex sensitivity (BRS) was measured before and after ouabain treatment. At baseline, BRS was similar in (mRen2)27 and mRen2.Lewis rats (0.49 ± 0.13 vs 0.37 ± 0.08 msec/mm Hg). BRS was decreased following ouabain injections in mRen2.Lewis animals (0.005 ± 0.01 msec/mm Hg; p < 0.05 vs baseline) but was unaffected in (mRen2)27 (0.37 ± 0.07 msec/mm Hg). Thus, an exacerbated pressor response was associated with suppression of the BRS in mRen2.Lewis rats. MD000232, MD002303, HL51952