Exp Mol Med.  2004 Jun;36(3):251-258.

Gene expression in uremic left ventricular hypertrophy: effects of hypertension andanemia

• Mak RH
• Chang SL
• Draksharapu A
• Pak YK

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.

Keyword

anemia; cardiac hypertrophy; hypertension; left ventricular hypertrophy; uremia

MeSH Terms

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