Effects of resibufogenin in experimental hypertension.
OBJECTIVE
There are two major pathophysiologic processes involved in the development of hypertension: (1) expanded extracellular fluid volume and (2) vasoconstriction. We have developed a model of preeclampsia in the rat, in which excessive volume expansion (VE) plays a role. These animals excrete increased amounts of the bufodienolide, marinobufagenin (MBG), even before their hypertension and proteinuria become established. Furthermore, their hypertension is corrected by administration of resibufogenin (RBG), a compound structurally similar to MBG.


METHODS
We studied two models of experimental hypertension in the nonpregnant animal, produced either by deoxycorticosterone acetate (DOCA)-salt administration or by angiotensin infusion.


RESULTS
RBG administered to the DOCA-salt rats lowered blood pressure and reduced proteinuria in the VE animals, but had no affect on the rats infused with angiotensin. Furthermore, although the production of superoxide anion in the aortas of both groups of hypertensive rats was increased over control, RBG reduced these levels to normal in the VE (DOCA-salt) animals only. RBG had no effect in the angiotensin-infused rats. The urinary excretion of angiotensinogen did not rise in VE-mediated hypertension, but did increase in the angiotensin-infused rats.


CONCLUSIONS
MBG plays an important role in the causation of hypertension in the VE rats, but not in the vasoconstrictive model. RBG is effective only in VE-mediated hypertension.
Danchuk
S
S
Section of Nephrology and Hypertension, Department of Medicine, Tulane University School of Medicine, New Orleans, LA, USA.
Sukhanov
S
S
Horvat
D
D
Uddin
M N
MN
Puschett
J B
JB
D000804:Angiotensin II / Q000494:pharmacology; D000808:Angiotensinogen / Q000652:urine; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002018:Bufanolides / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D003404:Creatinine / Q000097:blood; D003900:Desoxycorticosterone; D004195:Disease Models, Animal; D006977:Hypertension, Renal / Q000139:chemically induced / Q000188:drug therapy*; D008297:Male; D008901:Mineralocorticoids; D011507:Proteinuria / Q000139:chemically induced / Q000188:drug therapy*; D051381:Rats; D011919:Rats, Inbred Strains; D012965:Sodium Chloride; D013481:Superoxides / Q000378:metabolism; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D002018:Bufanolides; D008901:Mineralocorticoids; D014662:Vasoconstrictor Agents; D000808:Angiotensinogen; D013481:Superoxides; D000804:Angiotensin II; C005734:bufogenin; C093896:marinobufagenin; D003900:Desoxycorticosterone; D012965:Sodium Chloride; D003404:Creatinine