Brain ouabain stimulates peripheral marinobufagenin via angiotensin II signalling in NaCl-loaded Dahl-S rats.
OBJECTIVE
In NaCl-loaded Dahl salt-sensitive (DS) rats the transient stimulation of brain endogenous ouabain (EO) precedes the increase in renal excretion of marinobufagenin (MBG), a vasoconstrictor and natriuretic. In hypertensive DS rats, EO raises blood pressure (BP) via an ATII-sensitive pathway. We hypothesized that an NaCl-induced increase in MBG is linked to the EO-stimulated ATII pathway.


METHODS
We studied the effects of 3 h of NaCl loading (17 mmol/kg, intraperitoneally) in male DS rats treated with antibodies to MBG or ouabain, or with losartan (25 mg/kg).


RESULTS
NaCl loading alone induced a transient stimulation of pituitary EO (22.4 +/- 1.8 versus 12.2 +/- 1.3 pmol/g) and ATII (39.4 +/- 2.8 versus 18.4 +/- 3.2 ng/g), a sustained increase in MBG excretion (5.2 +/- 0.6 versus 1.1 +/- 0.2 pmol/h), a 40% inhibition of the renal sodium pump, a natriuretic response, a 35 mmHg increase in systolic BP, and an increase in adrenocortical ATII and MBG levels and in plasma norepinephrine. The anti-MBG antibody reduced the natriuresis (36%) and BP (40 mmHg), and restored renal sodium pump activity. The anti-ouabain antibody prevented the increase in pituitary ATII, reduced MBG excretion, natriuresis and BP, increased sodium pump activity, and prevented increases in plasma norepinephrine, pituitary and adrenocortical ATII, and adrenocortical MBG. Losartan mimicked the effects of the anti-ouabain antibody, but did not affect the excretion of EO. In adrenocortical cells of DS rats, ATII stimulated MBG secretion, and losartan blocked this effect.


CONCLUSIONS
In response to NaCl loading, brain EO, via an AT1 receptor pathway and probably via sympathetic activation, stimulates adrenocortical MBG, which inhibits the renal sodium pump and elevates BP.
Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA.
Olga V
OV
Fedorova
Natalia I
NI
Agalakova
Mark I
MI
Talan
Edward G
EG
Lakatta
Alexei Y
AY
Bagrov
D000302:Adrenal Cortex / Q000737:chemistry / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D000804:Angiotensin II / Q000032:analysis / Q000378:metabolism*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D001923:Brain Chemistry; D002018:Bufanolides / Q000097:blood / Q000494:pharmacology* / Q000652:urine; D002478:Cells, Cultured; D019808:Losartan / Q000494:pharmacology; D008297:Male; D009318:Natriuresis / Q000187:drug effects; D009638:Norepinephrine / Q000097:blood; D010042:Ouabain / Q000097:blood / Q000494:pharmacology* / Q000652:urine; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D020303:Rats, Inbred Dahl; D012083:Renin / Q000097:blood; D012965:Sodium Chloride / Q000494:pharmacology* / Q000652:urine; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D047228:Angiotensin II Type 1 Receptor Blockers; D000906:Antibodies; D002018:Bufanolides; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; C093896:marinobufagenin; D012965:Sodium Chloride; D010042:Ouabain; D012083:Renin; D000254:Sodium-Potassium-Exchanging ATPase; D019808:Losartan; D009638:Norepinephrine