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

Abstract

Ouabain increases vascular resistance and may induce hypertension by inhibiting the Na + pump. The effects of 0.18 and 18 µg/kg, and 1.8 mg/ kg ouabain pretreatment on the phenylephrine (PHE; 0.1, 0.25 and 0.5 µg, in bolus)-evoked pressor responses were investigated using anesthetized normotensive (control and uninephrectomized) and hypertensive (1K1C and DOCA-salt treated) rats. Treatment with 18 µg/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 µg/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 µg/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. Correspondence

The α2-isoform of Na-K-ATPase mediates ouabain-induced hypertension in mice and increased vascular contractility in vitro

“…Thus it is reasonable to assume that administration of low concentrations of ouabain did not result in serum levels that are sufficient to induce hypertension in mice. Consistent with the previous studies in rats, the acute pressor effect of ouabain was observed in anesthetized mice (25). It occurred following intravenous administration of the same dose of ouabain that induced hypertension in wild-type mice following prolonged administration.…”

Ouabain-induced hypertension is accompanied by increases in endothelial vasodilator factors

“…Higher micromolar concentrations of ouabain induce contractions by a direct action on the vascular smooth muscle and/or by releasing norepinephrine from the perivascular adrenergic nerve endings (35,42). In the anesthetized normotensive rat, acutely administered ouabain at doses of 10 and 30 nmol/kg iv can increase arterial pressure, in part, by causing the release of norepinephrine from peripheral nerve endings (2,44). However, the reactivity of phenylephrine is reduced in some vascular beds following long-term ouabain treatment.…”

Hypertensive effects of the iv administration of picomoles of ouabain

“…In some rat models of hypertension, including the SHR model (28), renovascular hypertension and L-NAMEinduced hypertension (29), acute ouabain administration increases blood pressure, whereas no change in blood pressure is observed in normotensive rats (14,30,31). These results suggest that the effects of ouabain are amplified in hypertensive conditions.…”

“…Acutely, ouabain in picomole quantities increases blood pressure (24,(28)(29)(30)(31), pressor and vascular reactivity to vasoconstrictor agents (14,24,(28)(29)(30)(31)40,41), and sympathoexcitatory activity (9,53). These effects of ouabain are due at least in part to activation of the central and peripheral renin-angiotensin system (31,28,(50)(51)(52).…”