Activated vitamin D attenuates left ventricular abnormalities induced by dietary sodium in Dahl salt-sensitive animals.
Observations in hemodialysis patients suggest a survival advantage associated with activated vitamin D therapy. Left ventricular (LV) structural and functional abnormalities are strongly linked with hemodialysis mortality. Here, we investigated whether paricalcitol (PC, 19-nor-1,25(OH)(2)D(2)), an activated vitamin D compound, attenuates the development of LV abnormalities in the Dahl salt-sensitive (DSS) rat and whether humans demonstrate comparable findings. Compared with DSS rats fed a high-salt (HS) diet (6% NaCl for 6 weeks), HS+PC was associated with lower heart and lung weights, reduced LV mass, posterior wall thickness and end diastolic pressures, and increased fractional shortening. Blood pressures did not significantly differ between the HS groups. Plasma brain natriuretic peptide levels, and cardiac mRNA expression of brain natriuretic peptide, atrial natriuretic factor, and renin were significantly reduced in the HS+PC animals. Microarray analyses revealed 45 specific HS genes modified by PC. In a retrospective pilot study of hemodialysis patients, PC-treated subjects demonstrated improved diastolic function and a reduction in LV septal and posterior wall thickness by echocardiography compared with untreated patients. In summary, PC attenuates the development of LV alterations in DSS rats, and these effects should be examined in human clinical trials.
Bodyak
Natalya
N
Cardiovascular Division and Division of Nephrology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
Ayus
Juan Carlos
JC
Achinger
Steven
S
Shivalingappa
Venkatesha
V
Ke
Qingen
Q
Chen
Yee-Shiuan
YS
Rigor
Debra L
DL
Stillman
Isaac
I
Tamez
Hector
H
Kroeger
Paul E
PE
Wu-Wong
Ruth R
RR
Karumanchi
S Ananth
SA
Thadhani
Ravi
R
Kang
Peter M
PM
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000235:genetics / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D004452:Echocardiography; D004872:Ergocalciferols / Q000494:pharmacology*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000503:physiopathology / Q000517:prevention & control*; D008297:Male; D020097:Natriuretic Peptide, Brain / Q000097:blood / Q000235:genetics; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D020303:Rats, Inbred Dahl; D006435:Renal Dialysis; D012982:Sodium, Dietary / Q000494:pharmacology*
D004872:Ergocalciferols; D012982:Sodium, Dietary; D020097:Natriuretic Peptide, Brain; C084656:paricalcitol; D009320:Atrial Natriuretic Factor