DISSOCIATION OF CARDIAC-HYPERTROPHY, MYOSIN HEAVY-CHAIN ISOFORM EXPRESSION, AND NATRIURETIC PEPTIDE PRODUCTION IN DOCA-SALT RATS

We examined the relationship between cardiac hypertrophy, myosin heavy chain (MHC) isoform expression, and production of atrial natriuretic factor (ANF) and brain natriuretic peptide (BNP) before and after the development of DOCA-salt hypertension. DOCA-salt rats exhibited signif icant left ventricular hypertrophy at the prehypertensive stage (1 wee k of treatment), without MHC isoform switch or change in natriuretic p eptide gene expression. In the hypertensive stage (5 weeks of treatmen t), pronounced left ventricular hypertrophy was observed, and this was characterized by an increase in beta-MHC protein, resulting in a swit ch from 90% alpha-MHC to 51% alpha-MHC and 49% beta-MHC. ANF and BNP m RNA levels and peptide content were significantly increased at this st age. Unexpectedly, the MHC isoform switch was evident in the nonhypert rophied right ventricle to the same degree as in the left ventricle. N atriuretic peptide production was also increased in the right ventricl e at 5 weeks of treatment, but to a lesser degree than in the left ven tricle. In contrast, in the hypertrophied left atrium there was no MHC isoform switch, while ANF and BNP mRNA levels were augmented. Plasma ANF was significantly increased in the prehypertensive stage; this was accompanied by a partial depletion of atrial ANF stores. Plasma BNP w as increased only in the hypertensive stage, reflecting an increase in ventricular BNP synthesis and secretion. These results suggest that I ) cardiac hypertrophy, MHC isoform expression, and stimulation of natr iuretic peptide production are processes that may be dissociated from each other; 2) increases in plasma ANF without a concomitant increase in plasma BNP reflect atrial hemodynamic overload, while increases in both ANF and BNP in plasma are associated with ventricular hypertrophy ; and 3) there exist differences in the storage, secretion, and proces sing patterns of ANF and BNP in the atria.