Effects of small doses of ouabain on the arterial blood pressure of anesthetized hypertensive and normotensive rats

Ouabain increases vascular resistance and may induce hypertension by inhibi ting the Na+ pump. The effects of 0.18 and IS mug/kg, and 1.8 mg/ kg ouabai n pretreatment on the phenylephrine (PHE; 0.1, 0.25 and 0.5 pg, in bolus)-e voked pressor responses were investigated using anesthetized normotensive ( control and uninephrectomized) and hypertensive (1K1C and DOCA-salt treated ) rats. Treatment with 18 mug/kg ouabain increased systolic and diastolic b lood pressure in all groups studied. However, the magnitude of this increas e was larger for the hypertensive 1K1C and DOCA-salt rats than for normoten sive animals, while the pressor effect of 0. 18 mug/kg ouabain was greater only in DOCA-salt rats. A very large dose (1.8 mg/kg) produced toxic effect s on the normotensive control but not on uninephrectomized. or 1K1C rats. R at tail vascular beds were perfused to analyze the effects of 10 nM ouabain on the pressor response to PHE. In all animals, 10 nM ouabain increased th e PHE pressor response, but this increase was larger in hypertensive DOCA-s alt rats than in normotensive and 1K1C rats. Results suggested that a) incr eases in diastolic blood pressure induced by 18 mug/kg ouabain were larger in hypertensive than normotensive rats; b) in DOCA-salt rats, smaller ouaba in doses had a stronger effect than in other groups; c) hypertensive and un inephrectomized rats were less sensitive to toxic doses of ouabain, and d) after treatment with 10 nM ouabain isolated tail vascular beds from DOCA-sa lt rats were more sensitive to the pressor effect of PRE than those from no rmotensive and 1K1C hypertensive rats. These data suggest that very small d oses of ouabain, which might produce nanomolar plasma concentrations, enhan ce pressor reactivity in DOCA-salt hypertensive rats, supporting the idea t hat endogenous ouabain may contribute to the increase and maintenance of va scular tone in hypertension.