DIFFERENTIAL REGULATION OF VENTRICULAR ADRENOMEDULLIN AND ATRIAL-NATRIURETIC-PEPTIDE GENE-EXPRESSION IN PRESSURE AND VOLUME OVERLOAD IN THERAT

1. Adrenomedullin is a recently discovered vasodilating and natriureti c peptide whose physiological and pathophysiological roles remain to b e established. Like atrial natiuretic peptide adrenomedullin is expres sed in the left ventricle, Ventricular expression of atrial natriureti c peptide is knowm to be markedly increased by volume or pressure over load. In this study we investigated whether ventricular expression of adrenomedullin is similarly stimulated under such conditions. 2. Ventr icular adrenomedullin and atrial natriuretic peptide mRNA levels as we ll as those of a loading central mRNA (glyceraldehyde-3-phosphate dehy drogenase) were quantified by Northern blot analysis in (a) rats with severe post-infarction heart failure induced by left coronary ligation at 30 days post-surgery and (b) in rats with pressure-related cardiac hypertrophy induced by aortic banding at several time points (0.5, 1 and 4 h, and 1, 4, 7 and 28 days) after surgery. Levels were compared with those in matched sham-operated controls. 3. The mRNA level of atr ial natriuretic peptide was markedly increased (8-10-fold) in the left ventricle of animals with post-infarction heart failure. In contrast, there was only a modest (40%) increase in the level of adrenomedullin mRNA, In rats with pressure-induced cardiac hypertrophy the ventricul ar level of atrial natriuretic peptide mRNA was again markedly increas ed (maximum 10-fold), The increase was first noticeable at 24 h post-b anding and persisted until 28 days. In contrast, there was no change i n adrenomedullin mRNA level compared with sham-operated rats at any ti me point. 4. Despite having similar systemic effects, the expression o f adrenomedullin and atrial natriuretic peptide in the left ventricle is differently regulated. The findings imply distinct roles for the tw o peptides. The results do not support an important role for ventricul ar adrenomedullin expression in the remodelling process that occurs du ring the development of cardiac hypertrophy but suggest that ventricul ar adrenomedullin participates in the local and/or systemic response t o heart failure.