The ouabain-dependent Na(+)-K+ pump and the brain renin-angiotensin system.
The present study investigated the role of ouabain-dependent inhibition of the Na(+)-K+ pump and stimulation of the brain renin-angiotensin system by looking at 1) the short-term and long-term effects of ouabain on arterial blood pressure, and 2) the acute and chronic effects of angiotensin II (ANG II) intraventricularly (i.c.v.) on the release of an endogenous inhibitor of the Na(+)-K+ pump. Ouabain infused subcutaneously in a dose of 1.5 mg.kg-1. 24 h-1 for 7 days did not affect arterial blood pressure in rats, whereas increases in both blood pressure and weight were observed in rats infused with ouabain at the same dose for a 4-week period. Plasma supernate obtained from pentobarbital-anesthetized dogs acutely treated with ANG II (1 microgram i.c.v. every 30 min for 2 h) induced a 44% decrease in the ouabain-sensitive 86Rb uptake by the rat tail artery which was prevented by pretreatment with saralasin i.c.v. Plasma supernate obtained from dogs that were infused for 4 days with ANG II (20 ng/min i.c.v.) and received saline as the drinking fluid also reduced by 34% the ouabain-sensitive 86Rb uptake by the rat tail artery. The present study provides evidence that chronic inhibition of the Na(+)-K+ pump for 4 weeks leads to the development of hypertension and that the release of an endogenous inhibitor of the Na(+)-K+ pump is implicated in the hypertension resulting from chronic stimulation of the brain angiotensin-system and an increase in sodium chloride intake.
Doursout
M F
MF
Department of Anesthesiology, Baylor College of Medicine, Houston, Texas 77030.
Chelly
J E
JE
Liang
Y Y
YY
Buckley
J P
JP
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D004285:Dogs; D005260:Female; D006973:Hypertension / Q000209:etiology / Q000503:physiopathology; D008297:Male; D010042:Ouabain / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012084:Renin-Angiotensin System / Q000502:physiology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000187:drug effects / Q000502:physiology*
D000804:Angiotensin II; D010042:Ouabain; D000254:Sodium-Potassium-Exchanging ATPase