1. We assessed the changes of atrial natriuretic peptide and brain natriuretic peptide gene expression associated with progression and regression of cardiac hypertrophy in renovascular hypertensive rats (RHR). 2. Two-kidney, one-clip hypertensive rats (6-week-old male Wistar) were made and studied 6 (RHR-1) and 10 weeks (RHR-2) after the procedure. Regression of cardiac hypertrophy was induced by nephrectomy at 6 weeks after constriction, and the nephrectomized rats were maintained further for 4 weeks (nephrectomized rat: NEP). Sham operation was performed, and the rats were studied after 6 (Sham-1) and 10 weeks (Sham-2). Atrial natriuretic peptide and brain natriuretic peptide gene expression in the left ventricle was analysed by Northern blotting. 3. Plasma atrial natriuretic peptide and brain natriuretic peptide were significantly higher in RHR-1 and RHR-2 than in Sham-1, Sham-2 and NEP. Atrial natriuretic peptide and brain natriuretic peptide mRNA levels in RHR-1 were approximately 7.2-fold and 1.8-fold higher than those in Sham-1, respectively, and the corresponding levels in RHR-2 were 13.0-fold and 2.4-fold higher than those in Sham-2, respectively. Atrial natriuretic peptide and brain natriuretic peptide mRNA levels of NEP were normalized. Levels of atrial natriuretic peptide and brain natriuretic peptide mRNA were well correlated positively with left ventricular weight/body weight ratios. There was a significant positive correlation between the levels of atrial natriuretic peptide and brain natriuretic peptide mRNA ( r = 0.86, P <0.01). 4. We conclude that the expression of atrial natriuretic peptide and brain natriuretic peptide genes is regulated in accordance with the degree of myocardial hypertrophy and that the augmented expression of these two natriuretic peptides may play an important role in the maintenance of cardiovascular haemodynamics in renovascular hypertension.
1. In order to clarify whether the myocardial dysfunction observed in diabetic-rat hearts is an intrinsic property of the myocytes or not, we investigated cardiac function and myocyte contractile function in diabetic rats 5 weeks after the injection of streptozotocin. 2. Maximal and minimal d P /d t and time constant of isovolumic pressure fall were measured using a micromanometer in diabetic and age-matched control rats. 3. Isolated myocytes were enzymically obtained from each rat heart and were stimulated at 1 Hz (37°C) in a buffer containing 1.5 mmol/l Ca 2+ . The images of myocyte contractions were recorded by a video system. Normalized maximal velocity of shortening (maximal velocity of cell shortening/resting cell length; s −1 ), normalized maximal velocity of relengthening (maximal velocity of cell relengthening/resting cell length; s −1 ) and extent of shortening [(twitch amplitude/resting cell length) × 100;%] were analysed by a digitalized computer as contractile functions of the myocyte. 4. The maximal and minimal d P /d t in diabetic rats (7876, 5341 mmHg/s) were significantly lower than those in control rats (9349, 7876 mmHg/s). The time constant of isovolumic pressure fall in diabetic rats (12.7 ms) was significantly greater than that in control rats (8.6 ms). Moreover, the normalized maximal velocity of shortening, normalized maximal velocity of relengthening and extent of shortening in myocytes from diabetic rats (1.40 s −1 , 1.38 s −1 , 9.5%) were significantly lower than those in myocytes from control rats (1.64 s −1 , 1.60 s −1 , 11.8%). 5. These results suggest that contractile impairment in this diabetic-rat heart model is mainly due to an intrinsic abnormality of the cardiac myocytes.