Article

Activated vitamin D attenuates left ventricular abnormalities induced by dietary sodium in Dahl salt-sensitive animals

Cardiovascular Division and Division of Nephrology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
Proceedings of the National Academy of Sciences (Impact Factor: 9.81). 11/2007; 104(43):16810-5. DOI: 10.1073/pnas.0611202104
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ABSTRACT 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.

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Available from: Juan Carlos Ayus, Jul 29, 2015
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    • "reports linking vitamin D deficiency to various other health outcomes including heart failure and SCD [28] [29]. Importantly, vitamin D sufficiency has been shown to exert protective effects on the vasculature by modulating and maintaining heart cell structure and function, while also attenuating the development of left ventricular alterations, as well as myocardial dysfunction [30] [31]. As mentioned previously, each single biomarker represents a separate patho-physiological aspect. "
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    • "In a rat model of 5/6 nephrectomy, a cardiorenal model that provokes myocardial remodeling including fibrosis, it was shown that that paricalcitol does not reduce but rather aggravates myocardial fibrosis and profibrotic gene expression [33] [34]. Bodyak et al. [13] also showed no effects on cardiac fibrosis in their study in hypertensive rats. So, the precise role of paricalcitol in myocardial fibrogenesis remains to be proven. "
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    • "More importantly, our data demonstrate that paricalcitol does not affect blood pressure in the uremic rats during the treatment period, suggesting that the effect of paricalcitol on improving endothelial function is independent of blood pressure control. Our observation is consistent with the finding made by Bodyak et al. [29] that paricalcitol attenuated the development of left ventricular abnormalities in the Dahl salt-sensitive rat (a different experimental model from the 5/6 nephrectomized uremic rats) without a significant effect on blood pressure. Karavalakis et al. [28] "
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