title: Hypertensive effects of the iv administration of picomoles of ouabain.
abstract: Ouabain, an endogenous digitalis compound, has been detected in nanomolar concentrations in the plasma of several mammals and is associated with the development of hypertension. In addition, plasma ouabain is increased in several hypertension models, and the acute or chronic administration of ouabain increases blood pressure in rodents. These results suggest a possible association between ouabain and the genesis or development and maintenance of arterial hypertension. One explanation for this association is that ouabain binds to the α-subunit of the Na(+) pump, inhibiting its activity. Inhibition of this pump increases intracellular Na(+), which reduces the activity of the sarcolemmal Na(+)/Ca(2+) exchanger and thereby reduces Ca(2+) extrusion. Consequently, intracellular Ca(2+) increases and is taken up by the sarcoplasmic reticulum, which, upon activation, releases more calcium and increases the vascular smooth muscle tone. In fact, acute treatment with ouabain enhances the vascular reactivity to vasopressor agents, increases the release of norepinephrine from the perivascular adrenergic nerve endings and promotes increases in the activity of endothelial angiotensin-converting enzyme and the local synthesis of angiotensin II in the tail vascular bed. Additionally, the hypertension induced by ouabain has been associated with central mechanisms that increase sympathetic tone, subsequent to the activation of the cerebral renin-angiotensin system. Thus, the association with peripheral mechanisms and central mechanisms, mainly involving the renin-angiotensin system, may contribute to the acute effects of ouabain-induced elevation of arterial blood pressure.
authors.affiliation: Departamento de Ciências Fisiológicas, Universidade Federal do Espírito Santo, Vitória, ES, Brasil. ale_padilha@hotmail.com
authors.forename: A S
authors.initials: AS
authors.lastname: Padilha
authors.forename: M
authors.initials: M
authors.lastname: Salaices
authors.forename: D V
authors.initials: DV
authors.lastname: Vassallo
authors.forename: P R
authors.initials: PR
authors.lastname: Batista
authors.forename: F D M
authors.initials: FD
authors.lastname: Siman
mesh_terms: D000804:Angiotensin II / Q000096:biosynthesis; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D002490:Central Nervous System / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000139:chemically induced* / Q000378:metabolism; D007275:Injections, Intravenous; D009638:Norepinephrine / Q000378:metabolism; D010042:Ouabain / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D051381:Rats; D012084:Renin-Angiotensin System / Q000187:drug effects; D000254:Sodium-Potassium-Exchanging ATPase / Q000187:drug effects / Q000502:physiology
chemical_list: D002316:Cardiotonic Agents; D000804:Angiotensin II; D010042:Ouabain; D007703:Peptidyl-Dipeptidase A; D000254:Sodium-Potassium-Exchanging ATPase; D002118:Calcium; D009638:Norepinephrine