High-phosphorus/zinc-free diet aggravates hypertension and cardiac dysfunction in a rat model of the metabolic syndrome.
BACKGROUND
Cardiac dysfunction is reported in patients with the metabolic syndrome. We assessed the effects of high-phosphorus and zinc-free diet on cardiovascular system in spontaneously hypertensive rats (SHR)/NDmcr-cp (SHR/cp), a rat model of the metabolic syndrome. We also investigated the effects of N-acetyl-L-cysteine (NAC), an antioxidant, on the development of cardiac dysfunction under such conditions.


METHODS
Male SHR/cp and control [Wistar Kyoto (WKY)] rats were divided into three groups and fed control diet (P 0.3% w/w, Zn 0.2% w/w) or high-phosphorus and zinc-free (P 1.2% w/w, Zn 0.0% w/w) diet. The latter group was treated with either NAC (1.5 mg/g per day) or vehicle from 6 to 18 weeks of age (n=6 or 8 for each group).


RESULTS
High-phosphate and zinc-free diet increased systolic blood pressure in both WKY and SHR/cp. Echocardiography showed that high-phosphate and zinc-free diet markedly reduced left ventricular systolic and diastolic function in SHR/cp. Histopathologically, the same diet induced severe myocardial fibrosis in SHR/cp, and this effect was prevented by NAC. Whereas treatment with NAC prevented diastolic dysfunction induced by the same diet in WKY, it only improved systolic function but not diastolic function in SHR/cp.


CONCLUSIONS
High-phosphate and zinc-free diet induced hypertension and cardiac dysfunction. These changes hamper the protective effects of NAC in the metabolic syndrome.


CONCLUSIONS
The present study showed that consumption of high-phosphorus and zinc-free diet increased the myocardial expression of connective tissue growth factor and reduced the expression of metallothionein, which enhanced the development of severe cardiac dysfunction in rats with the metabolic syndrome. The results suggest that the metabolic syndrome seems to aggravate cardiac dysfunction and hamper the protective effects of antioxidant, NAC.
Graduate School of Regional Innovation Studies, Mie University, Tsu 514-8507, Japan.
Yuka
Y
Suzuki
Shingo
S
Mitsushima
Ai
A
Kato
Takanori
T
Yamaguchi
Sahoko
S
Ichihara
D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001794:Blood Pressure; D003094:Collagen / Q000378:metabolism; D055513:Connective Tissue Growth Factor / Q000378:metabolism; D003971:Diastole; D004195:Disease Models, Animal; D005355:Fibrosis; D006973:Hypertension / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D024821:Metabolic Syndrome / Q000150:complications* / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D008668:Metallothionein / Q000378:metabolism; D009206:Myocardium / Q000473:pathology; D016226:Phosphorus, Dietary / Q000009:adverse effects*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013599:Systole; D018487:Ventricular Dysfunction, Left / Q000209:etiology* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D016277:Ventricular Function, Left; D015032:Zinc / Q000172:deficiency*
D000975:Antioxidants; C526316:CCN2 protein, rat; D016226:Phosphorus, Dietary; D055513:Connective Tissue Growth Factor; D003094:Collagen; D008668:Metallothionein; D015032:Zinc; D000111:Acetylcysteine
Antioxidant; Cardiac dysfunction; Fibrosis; Hypertrophy; Metabolic syndrome