Endogenous bufadienolide mediates pressor response to ethanol withdrawal in rats.
An endogenous natriuretic and vasoconstrictor Na/K-ATPase inhibitor, marinobufagenin (MBG), is implicated in NaCl-induced hypertension and in ethanol addiction. In rats, MBG suppresses voluntary alcohol intake, while immunization against MBG induces alcohol-seeking behavior. Since alcohol withdrawal is associated with elevation of blood pressure (BP) and renal sodium retention, we hypothesized that MBG mediates pressor response to ethanol withdrawal. In male Sprague-Dawley rats, forced ethanol intake (20% v/v, 2.8+/-0.2 g/day for 7 days) did not affect BP and MBG excretion. Ethanol withdrawal was associated with a 21 mm Hg increase in BP, a 10% decrease in hematocrit, and a three-fold increase in renal MBG excretion. In vivo administration of anti-MBG antibody to rats prevented withdrawal-induced BP elevation. Therefore, MBG mediates pressor response to ethanol withdrawal, and may link mechanisms of ethanol dependence and hypertension.
Laboratory of Cardiovascular Science, National Institute on Aging/NIH, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA.
Vladimir A
VA
Kashkin
Edwin E
EE
Zvartau
Olga V
OV
Fedorova
Yakov Y
YY
Bagrov
Edward G
EG
Lakatta
Alexei Y
AY
Bagrov
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002018:Bufanolides / Q000627:therapeutic use* / Q000652:urine; D002492:Central Nervous System Depressants; D000431:Ethanol; D006400:Hematocrit; D008297:Male; D010042:Ouabain / Q000652:urine; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000652:urine; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy* / Q000503:physiopathology*; D014662:Vasoconstrictor Agents / Q000627:therapeutic use* / Q000652:urine
D002018:Bufanolides; D002492:Central Nervous System Depressants; D014662:Vasoconstrictor Agents; D000431:Ethanol; C093896:marinobufagenin; D010042:Ouabain; D012964:Sodium