title: Therapeutic effects of vitamin D analogs on cardiac hypertrophy in spontaneously hypertensive rats.
abstract: Vitamin D inhibits renin expression and blocks the compensatory induction of renin associated with the use of renin-angiotensin system inhibitors. Here we test the therapeutic effects of two commonly used vitamin D analogs and their combination with losartan on the development of left ventricular hypertrophy. One-month-old male spontaneously hypertensive rats were treated with vehicle, losartan, paricalcitol, doxercalciferol, a combination of losartan and paricalcitol, or a combination of losartan and doxercalciferol for 2 months. Blood pressure was markedly reduced by losartan, but not by paricalcitol or doxercalciferol alone. Echocardiograpy demonstrated a 65 to 80% reduction in left ventricular wall thickness with losartan, paricalcitol, or doxercalciferol monotherapy and almost complete prevention of left ventricular hypertrophy with the combination therapies. Attenuation of cardiac and cardiomyocyte hypertrophy, and suppression of atrial and brain natriuretic peptides, were most marked in the combination therapy groups. These changes were well correlated with left ventricular gene and microRNA expression profiles in the different treatment groups. Renal and cardiac renin expression was markedly increased in losartan-treated animals, but nearly normalized with combination therapy. The same vitamin D analogs suppressed plasma renin activity in patients receiving chronic hemodialysis. These data demonstrate that vitamin D analogs have potent antihypertrophic activity in part via suppression of renin in the kidney and heart, and combination of these analogs with losartan achieves much better therapeutic effects because of the blockade of the compensatory renin increase.
authors.affiliation: Laboratory of Metabolic Disease Research and Drug Development, Shengjing Hospital, China Medical University, Shenyang, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Kong
authors.forename: Gene H
authors.initials: GH
authors.lastname: Kim
authors.forename: Minjie
authors.initials: M
authors.lastname: Wei
authors.forename: Tao
authors.initials: T
authors.lastname: Sun
authors.forename: George
authors.initials: G
authors.lastname: Li
authors.forename: Shu Q
authors.initials: SQ
authors.lastname: Liu
authors.forename: Xinmin
authors.initials: X
authors.lastname: Li
authors.forename: Ishir
authors.initials: I
authors.lastname: Bhan
authors.forename: Qun
authors.initials: Q
authors.lastname: Zhao
authors.forename: Ravi
authors.initials: R
authors.lastname: Thadhani
authors.forename: Yan Chun
authors.initials: YC
authors.lastname: Li
mesh_terms: D000368:Aged; D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use; D004872:Ergocalciferols / Q000627:therapeutic use*; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000188:drug therapy* / Q000473:pathology; D019808:Losartan / Q000627:therapeutic use; D008297:Male; D046228:Microarray Analysis; D008875:Middle Aged; D011897:Random Allocation; D051381:Rats; D011918:Rats, Inbred SHR; D012083:Renin / Q000097:blood; D014807:Vitamin D / Q000031:analogs & derivatives / Q000627:therapeutic use; D014815:Vitamins / Q000627:therapeutic use
chemical_list: D000959:Antihypertensive Agents; D004872:Ergocalciferols; D014815:Vitamins; D014807:Vitamin D; C042533:1 alpha-hydroxyergocalciferol; C084656:paricalcitol; D012083:Renin; D019808:Losartan