Oral treatment with the Crataegus special extract WS® 1442 inhibits cardiac hypertrophy in rats with DOCA-salt or aortic banding induced hypertension

Cardiac hypertrophy (CH) is an adaptive enlargement of the myocardium in response to diverse pathophysiological stimuli. Whereas this process is generally a beneficial response that temporarily augments cardiac output, sustained hypertrophy often becomes maladaptive and is a leading cause for the development of heart failure. Activation of the protein phosphatase calcineurin is discussed as a major intracellular signaling pathway that contributes to the growth of cardiomyocytes. We have previously observed that WS® 1442, a special extract from leaves with flowers of Crataegus ssp., inhibits the enzymatic activity of calcineurin. Thus, it was the aim of the present study to evaluate if WS® 1442 affects the development of CH in animal models of hypertension. Hypertension and subsequent CH was induced in rats by aortic bending (AB) or administration of deoxycorticosterone (DOCA) in combination with NaCl/KCl-substituted drinking water. Animals were treated orally for a period of 14 (AB) or 28 days (DOCA-salt) with vehicle (0.2% agar suspension) or WS® 1442 (100 and 300mg/kg/day). On the final day, animals were anaesthetized and blood pressure (BP) and heart rate were measured following cannulation of the carotic artery. After euthanization, the heart was removed and the weights of the entire heart and the left ventricle were obtained. In both experimental models a marked increase of BP as well as enlargement of the heart and the left ventricle were observed. Treatment with WS® 1442 dose-dependently lowered the pathologically increased BP but had no effect on the BP in normal control animals. In parallel with the reduction of the BP development of cardiac hypertrophy was inhibited. The present study demonstrates that oral treatment of rats with WS® 1442 prevents development of CH induced by primary or secondary hypertension and thus supports its therapeutic use in the treatment of mild forms of heart failure.