Different Effects of in Vivo Ouabain and Digoxin on Renal Artery Function and Blood Pressure in the Rat

Abstract

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 EC50sfor KCI and the peak caffeine contractures were not different. KCI contractures were not affected by 5 ,aM prazosin. Phenylephrine contractures were increased marginally in ouabain-infused rats, while acetylcholine-induced relaxation was normal. /n 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 ,ug/kg/day, n= 23), but not digoxin (30 ,ug/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 sys-

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

“…As previously demonstrated, long-term treatment with ouabain induces the development of a time-dependent hypertension (10,21,23,26,32,45,54) as well as regional changes in the ouabain-sensitive sodium pump activity and expression of the ␣-isoforms (45). This hypertension is also associated with a reduction of phenylephrine-induced contractile activity in the thoracic aorta, but not in caudal arteries, and with an increase in the negative endothelial modulation of the actions of phenylephrine in both arteries (45).…”

“…It has been suggested that alterations in the activity of the sodium pump might be involved in the genesis or maintenance of hypertensive states (3, 33). Additionally, the hypertension induced by ouabain treatment has been associated with actions in the central nervous system that increase sympathetic activity by activation of the central renin-angiotensin system and impair the arterial baroreceptor reflex (22, 23) and associated with actions in the periphery that produce changes in responsiveness to contractile agents (10,26,45).In some isolated vascular preparations, acutely administered ouabain, at nanomolar concentrations, can enhance the actions of phenylephrine (43). 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).…”

“…nitric oxide; endothelial-dependent hyperpolarizing factor; phenylephrine THE PLASMA LEVELS of an endogenous circulating Na ϩ -K ϩ -ATPase inhibitor, characterized as ouabain or a closely related compound (17,36), are increased in several animal models of hypertension (19,39), as well as in human essential hypertension (20). Several studies have shown that chronic administration of ouabain induces hypertension, an effect that seems to be linked to the inhibition of the Na ϩ -K ϩ -ATPase (10,22,23,45,54), although sodium pump inhibition seems not to be the exclusive mechanism of the ouabain-hypertensive effect (26,31,32,52). This enzyme is found in most eukaryotic cells and is the main system involved in the maintenance of sodium homeostasis and the membrane potential, essential factors for controlling vascular tone and blood pressure.…”

“…It has been suggested that alterations in the activity of the sodium pump might be involved in the genesis or maintenance of hypertensive states (3, 33). Additionally, the hypertension induced by ouabain treatment has been associated with actions in the central nervous system that increase sympathetic activity by activation of the central renin-angiotensin system and impair the arterial baroreceptor reflex (22, 23) and associated with actions in the periphery that produce changes in responsiveness to contractile agents (10,26,45).…”

“…, although sodium pump inhibition seems not to be the exclusive mechanism of the ouabain-hypertensive effect (26,31,32,52). This enzyme is found in most eukaryotic cells and is the main system involved in the maintenance of sodium homeostasis and the membrane potential, essential factors for controlling vascular tone and blood pressure.…”