Control of cardiomyocyte gene expression as drug target

Pressure overload of the heart is associated with a perturbed gene expressi on of the cardiomyocyte leading to an impaired pump function. The ensuing n euro-endocrine activation results in disordered influences of angiotensin I I and catecholamines on gene expression. To assess whether angiotensin II t ype 1 receptor inhibition can also counteract a raised sympathetic nervous system activity, spontaneously hypertensive rats fed a hypercaloric diet we re treated with eprosartan (daily 90 mg/kg body wt) and cardiovascular para meters were monitored with implanted radiotelemetry pressure transducers. B oth, blood pressure and heart rate were increased (p < 0.05) by the hyperca loric diet. Although eprosartan reduced (p < 0.05) the raised systolic and diastolic blood pressure, the diet-induced rise in heart rate was blunted o nly partially. In addition to drugs interfering with the enhanced catechola mine influence, compounds should be considered that selectively affect card iomyocyte gene expression via 'metabolic' signals.