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

L.V Rossoni,D.V Vassallo,V.D Pinto

doi:10.1590/s0100-879x2001000800014

L.V Rossoni, D.V Vassallo + Show 1 more

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https://doi.org/10.1590/s0100-879x2001000800014

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Abstract

Ouabain increases vascular resistance and may induce hypertension by inhibiting the Na+ pump. The effects of 0.18 and 18 microg/kg, and 1.8 mg/kg ouabain pretreatment on the phenylephrine (PHE; 0.1, 0.25 and 0.5 microg, in bolus)-evoked pressor responses were investigated using anesthetized normotensive (control and uninephrectomized) and hypertensive (1K1C and DOCA-salt treated) rats. Treatment with 18 microg/kg ouabain increased systolic and diastolic blood pressure in all groups studied. However, the magnitude of this increase was larger for the hypertensive 1K1C and DOCA-salt rats than for normotensive animals, while the pressor effect of 0.18 microg/kg ouabain was greater only in DOCA-salt rats. A very large dose (1.8 mg/kg) produced toxic effects on the normotensive control but not on uninephrectomized or 1K1C rats. Rat 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 the PHE pressor response, but this increase was larger in hypertensive DOCA-salt rats than in normotensive and 1K1C rats. Results suggested that a) increases in diastolic blood pressure induced by 18 microg/kg ouabain were larger in hypertensive than normotensive rats; b) in DOCA-salt rats, smaller ouabain doses had a stronger effect than in other groups; c) hypertensive and uninephrectomized rats were less sensitive to toxic doses of ouabain, and d) after treatment with 10 nM ouabain isolated tail vascular beds from DOCA-salt rats were more sensitive to the pressor effect of PHE than those from normotensive and 1K1C hypertensive rats. These data suggest that very small doses of ouabain, which might produce nanomolar plasma concentrations, enhance pressor reactivity in DOCA-salt hypertensive rats, supporting the idea that endogenous ouabain may contribute to the increase and maintenance of vascular tone in hypertension.

Highlights

Previous reports have shown that ouabain pretreatment of normotensive rats enhances arterial blood pressure and vasopressor responses to vasoconstrictor agents in vivo and in vitro [1,2]
Results suggested that a) increases in diastolic blood pressure induced by 18 μg/kg ouabain were larger in hypertensive than normotensive rats; b) in deoxycorticosterone acetate (DOCA)-salt rats, smaller ouabain doses had a stronger effect than in other groups; c) hypertensive and uninephrectomized rats were less sensitive to toxic doses of ouabain, and d) after treatment with 10 nM ouabain isolated tail vascular beds from DOCA-salt rats were more sensitive to the pressor effect of PHE than those from normotensive and 1K1C hypertensive rats
Systolic and diastolic blood pressure were reduced in all models and this reduction was significantly larger in the 1K1C and DOCA-salt groups (Table 1)

Summary

Introduction

Previous reports have shown that ouabain pretreatment of normotensive rats enhances arterial blood pressure and vasopressor responses to vasoconstrictor agents in vivo and in vitro [1,2]. The sensitization induced by ouabain was observed in spontaneously hypertensive rats (SHR) [1]. The SHR presented enhanced pressor responses after administration of very low doses of ouabain, which were not enough to induce the same effect in normotensive rats [1]. We demonstrated that both 100 μM and 10 nM ouabain enhance the vasoactive responses elicited by phenylephrine in rat tail arteries [1,2]. In these preparations the enhancement of the vasoconstrictor responses to phenylephrine was greater in SHR [1]

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