Gene expression in uremic left ventricular hypertrophy: effects of hypertension andanemia.
- Author:
Robert H MAK
1
;
Stella L CHANG
;
Aparna DRAKSHARAPU
;
Youngmi Kim PAK
Author Information
1. Division of Pediatric Nephrology, Department of Pediatrics, Oregon Health and Science University, Portland, OR 9720, USA.
- Publication Type:Original Article
- Keywords:
anemia;
cardiac hypertrophy;
hypertension;
left ventricular hypertrophy;
uremia
- MeSH:
Actins/genetics/metabolism;
Anemia/*complications/drug therapy/metabolism;
Animals;
Atrial Natriuretic Factor/genetics/metabolism;
Erythropoietin/pharmacology/therapeutic use;
*Gene Expression;
Heart Ventricles/chemistry/drug effects/pathology;
Hydralazine/pharmacology/therapeutic use;
Hypertension/*complications/drug therapy/metabolism;
Hypertrophy, Left Ventricular/etiology/*genetics/metabolism;
Male;
Peptidyl-Dipeptidase A/genetics/metabolism;
RNA, Messenger/analysis/metabolism;
Rats;
Rats, Sprague-Dawley;
Transforming Growth Factor beta/genetics/metabolism;
Uremia/etiology/*genetics/metabolism
- From:Experimental & Molecular Medicine
2004;36(3):251-258
- CountryRepublic of Korea
- Language:English
-
Abstract:
Hypertension and anemia may be causes of left ventricular hypertrophy (LVH) in uremia but the molecular mechanism is not known. Uremia was induced in male Spraugue Dawley rats by 5/6 nephrectomy. The following groups of rats were studied for 6 weeks; uremic rats (U) fed ad. lib., control rats (C) pair-fed with U, U rats given hydralazine (100 mg/kg/day) (UH), U rats given erythropoietin (48U/kg/week, i.p.) (UE). Both diastolic and mean arterial pressures are higher (P<0.01) in U and UE compared with C whereas both pressures in UH were normalized. Hemoglobin in U was lower than in C, and was normalized in UE. U, UH and UE had higher heart weight/body weight ratios (HW/BW) as well as left ventricular weight/body weight ratios (LV/BW) compared with C (P<0.01). Compared with U, UH has lower HW/BW and LV/BW (P <0.05) and UE has normal HW/BW but lower LV/BW than U (P<0.05). To see if the gene expression in uremic LVH is similar to that described in pressure overload LVH in which mRNA levels of angiotensin converting enzyme (ACE), transforming growth factor-beta1 (TGF-beta1), atrial natriuretic factors (ANF) and skeletal alpha-actin were increased, we measured these mRNA levels by Northern analysis. TGF-beta, ACE and alpha-actin mRNA levels were not changed in all 4 groups. ANF mRNA in U and UE was increased 3 fold over C, and normalized in UH. Treatment of anemia with erythropoietin improved uremic LVH but did not change ANF mRNA; whereas treatment of hypertension with hydralazine normalized ANF mRNA but did not completely correct uremic LVH. Thus, gene expression in uremic LVH is distinct from that in pressure- overload LVH, suggesting that other unidentified factor(s) might be involved in uremic LVH.
