Effect of parathyroidectomy on cardiac fibrosis and apoptosis: possible role of aldosterone.
OBJECTIVE
It has been demonstrated that parathyroidectomy prevents left ventricular hypertrophy in uremic animals. Although this effect may be mediated by direct actions of parathormone (PTH), it may also be exerted through regulation of profibrotic factors such as aldosterone. In adrenal cortex cell cultures, PTH increases aldosterone release. The objective of this work is to assess the effect of parathyroidectomy on aldosterone levels and on cardiac fibrosis and apoptosis in uremic rats.


METHODS
Four groups of rats were studied: C, control; 5/6Nx, 5/6 nephrectomy; PTx, parathyroidectomy, and 5/6NxPTx, 5/6 nephrectomy plus parathyroidectomy. Thirty days after the last surgical procedure the animals were sacrificed. Serum creatinine, ionized calcium, aldosterone, PTH, cardiac weight, fibrosis and apoptosis were measured.


RESULTS
Serum creatinine levels were significantly higher in 5/6Nx and 5/6NxPTx groups (1.62 +/- 0.21 and 1.38 +/- 0.15 mg/dl) than in C and PTx groups (0.66 +/- 0.02 and 0.47 +/- 0.01 mg/dl, p < 0.001). Potassium levels were significantly higher in the 5/6Nx and 5/6NxPTx groups (5.2 +/- 0.3 and 5.4 +/- 0.3 mg/dl) than in the C group (4.3 +/- 0.06 mg/dl, p < 0.05). Values in 5/6Nx and 5/6NxPTx groups were not significantly different from each other. PTH levels were significantly higher in the 5/6Nx group (470.5 +/- 156.3 microg/ml) than in the controls (102.3 +/- 14.3 microg/ml). PTH levels in the PTx group (1.78 +/- 0.52 microg/ml) and in the 5/6NxPTx group (81.64 +/- 32.15 microg/ml) were similar to control values. Ionized calcium was lower in PTx and 5/6NxPTx groups (0.80 +/- 0.07 and 0.89 +/- 0.07 mmol/l) as compared with C and 5/6Nx groups (1.14 +/- 0.01 and 0.96 +/- 0.01 mmol/ l, p < 0.01). The heart weight as percentage of the body weight increased significantly in 5/6Nx animals (4.20 +/- 0.15%) compared to the C group (3.41 +/- 0.27%, p < 0.05); parathyroidectomy reversed the heart weight increment in the 5/6NxPTx animals (3.58 +/- 0.16%). Myocardial fibrosis was significantly higher in the 5/6Nx group (12.5 +/- 1.1%) than in the C group (7.3 +/- 1.5%, p < 0.001); in the 5/6NxPTx animals fibrosis returned towards control values (8.9 +/- 0.2%). Myocardial apoptosis rose significantly in 5/6Nx animals (24.3 +/- 1.2%) compared to the C group (6.7 +/- 0.83%, p < 0.001); parathyroidectomy reversed the apoptosis in the 5/6NxPTx animals (10.4 +/- 0.49%). Aldosterone levels increased significantly in the 5/6Nx group (2,461 +/- 257 pg/ml) compared to the C group (703 +/- 81 pg/ml, p < 0.001); in the 5/6NxPTx animals aldosterone levels were below control values (509 +/- 99 pg/ml).


CONCLUSIONS
Uremia was associated to myocardial hypertrophy, fibrosis and apoptosis. Surgically induced hypoparathyroidism prevented the development of these disorders. Our results suggest that in the remnant kidney rat model myocardial hypertrophy, fibrosis, and apoptosis are mediated by high circulating aldosterone levels. Aldosterone, in turn, may be regulated by PTH.
Unidad de Investigación Médica en Enfermedades Nefrológicas, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Ciudad de México, México, DF. ernesto.rodriguez@imss.gob.mx
Ernesto
E
Rodríguez-Ayala
Marcela
M
Avila-Díaz
Enrique
E
Foyo-Niembro
Dante
D
Amato
Eduardo
E
Ramirez-San-Juan
Ramón
R
Paniagua
D000450:Aldosterone / Q000097:blood*; D000818:Animals; D017209:Apoptosis; D006332:Cardiomegaly / Q000209:etiology / Q000517:prevention & control; D005355:Fibrosis; D006321:Heart / Q000503:physiopathology*; D007011:Hypoparathyroidism / Q000209:etiology / Q000503:physiopathology; D008297:Male; D009206:Myocardium / Q000473:pathology*; D009392:Nephrectomy; D009929:Organ Size; D016105:Parathyroidectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D014511:Uremia / Q000150:complications / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*
D000450:Aldosterone