Neurohumoral factors during transition from left ventricular hypertrophy to failure in Dahl salt-sensitive rats

The relationship between the reduction in the positive inotropic effects (PIE) of beta-adrenergic stimulation and the level of systemic and tissue neurohumoral factors during the course from left ventricular (LV) hypertrophy to congestive heart failure (CHF) was studied in Dahl salt-sensitive rat (DS) CHF model. Control studies were performed in age-matched Dahl salt-resistant (DR) rats. In DS rats at CHF stage, plasma atrial natriuretic peptide (ANP) and norepinephrine (NE) levels were elevated markedly and myocardial NE level was decreased compared with those in the age-matched DR rats. On the other hand, at the hypertrophy stage, we observed no significant differences in plasma ANP or NE level between the two strains in spite of decrease in myocardial NE concentration. The PIE induced by isoproterenol was reduced at the stage of compensatory LV hypertrophy, which was followed by further reduction of PIE at CHF stage. The results distinctively indicate that beta-adrenergic desensitization in the myocardium which was accompanied with the abnormalities in local sympathoneuronal regulation begins during mechanically compensated LV hypertrophy and precedes systemic augmentation of sympathomimetic hormones.