[Spironolactone protection from hydralazine-induced stress in the rat myocardium].
OBJECTIVE
We wished to verify the possible protective action of spironolactone (SPIRO), through its blocking action of slow calcium channels, in what concerns behavioural, morphologic, histochemical and ultrastructural alterations caused by experimental exposure to hydralazine (HZ), due to the excess release of catecholamines and the cellular influx of calcium.


METHODS
Forty-eight adult male Wistar rats [correction of mice] were divided into 4 groups. The control group (CON) was administered olive oil for 4 days and distilled water i.v. on the last day, the hydralazine group (HZ) was administered olive oil for 4 days and 40 mg/kg i.v. of hydralazine on the last day; the spironolactone group (SPIRO) was administered 20 mg/kg of spironolactone diluted in olive oil for 4 days and distilled water on the last day; and the hydralazine with spironolactone group (HZ + SPIRO) was administered 20 mg/kg of spironolactone diluted in olive oil for 4 days and 40 mg/kg i.v. of hydralazine on the last day. The rats [correction of mice] were dissected and fragments of the myocardium removed for electron microscopy, and suprarenal fragments removed for light microscopy. Mitochondrial alterations characterised by ridge edema, lysis and vacuolisation (Cristolysis rate = damaged mitochondria/total mitochondria) were considered in the ultrastructural study.


RESULTS
Light microscopy of the HZ group showed intense depletion of lipids in the cortical region of the suprarenals. The HZ + SPIRO group did not present significant alterations and was similar in appearance to the CON group. The ultrastructural study of the myocardium revealed the following rates of Cristolysis: CON group = 5.8%, HZ group = 91.9%, SPIRO group = 10.9%, HZ + SPIRO group = 10.2%*. (* = p < 0.001 chi-square test).


CONCLUSIONS
The use of spironolactone in a model of stress induced by hydralazine caused: 1. Myocardial protection shown by reduced lesion of cardiomyocytes; 2. Protection of the suprarenals.
Póvoa
R
R
Cardiologia Experimental, Escola Paulista de Medicina, UNIFESP, São Paulo, Brasil.
Costa
A
A
Luna Filho
B
B
Ferreira Filho
C
C
Bombig
M T
MT
Murad
N
N
Ferreira
C
C
D000311:Adrenal Glands / Q000187:drug effects / Q000473:pathology; D000818:Animals; D000959:Antihypertensive Agents; D004353:Drug Evaluation, Preclinical; D006321:Heart / Q000187:drug effects*; D006830:Hydralazine; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists / Q000627:therapeutic use*; D009206:Myocardium / Q000648:ultrastructure*; D051381:Rats; D017208:Rats, Wistar; D013148:Spironolactone / Q000627:therapeutic use*; D013312:Stress, Physiological / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*
D000959:Antihypertensive Agents; D000451:Mineralocorticoid Receptor Antagonists; D006830:Hydralazine; D013148:Spironolactone
Protecção pela espironolactona do estresse pela hidralazina em miocárdio de ratos.