INCREASED COLLAGEN-(I) MESSENGER-RNA IN A LDOSTERONE-SALT CARDIOPATHY

Myocardial fibrosis as a consequence of systemic hypertension is a det erminant factor in alteration of cardiac function. It has been postula ted that this fibrous reaction is under the influence of an elevation of blood aldosterone. To gain further insight into the mechanisms that result in an accumulation of cardiac collagen, we used a model of ald osterone-salt-induced hypertension in rat. Uninephrectomized male Wist ar rats weighting 200 g were perfused with 0.75 mug/hr aldosterone and received 1 % NaCl + 0.3 % KCl in the drinking water for 2 months. Res ults : 1-degrees) Arterial hypertension was evidenced as soon as 15 da ys and reached 40 % at 2 months. 2-degrees) The left ventricle (LV) wa s hypertrophied by 45 % at 2 months and its relative content in mRNA c oding for the beta-isoform of the myosin heavy chain was increased by 142 %. 3-degrees). The microscopic examination of hemalun-eosin staine d LV showed a number of important foci of proliferating non-muscular c ells, of inflammatory aspect. 4-degrees) The LV collagen concentration as measured by hydroxyproline assay was not changed whereas an histol ogical study done on Sirius red-stained slides showed that the interst itial and perivascular collagen network was more important in treated rats. 5-degrees) The abundance of mRNAs coding for the alpha1 chain of type I collagen was increased by 60 %. Our results suggest that the f ibrous response involves a pretranslational regulation of collagen syn thesis.