Coronary Endothelial Function During the Development of Cardiac Hypertrophy: Insights From Pharmacological Intervention Studies

Abstract

Extensive clinical and experimental studies have shown the chronic heart failure/hypertrophy leads to a reduced coronary endothelial (CEC) function both at rest and in response to stimuli. Recently we employed a rat model of selective right ventricular hypertrophy (RVH) and found that the CEC function in right coronaries was significantly increased prior to the development of RVH, while the left coronaries from the unaffected left ventricle was not altered. As cardiac hypertrophy developed and worsened, marked depression of right CEC function was noted. To further investigate the significance of coronary endothelial function and NO production during the development of RVH, we studied the effects of both early (prevention) and late (rescue) treatments with a natural product (garlic) or a standard statin (rosuvastatin, RS), which have been previously shown to upregulate the endothelial/NO function. Oral treatment with 1% garlic supplemented diet either 1 day before or 1 day after the induction of RVH showed significant preservation of CEC function and prevention of RVH. Similar treatments with garlics without its active ingredient, allicin, failed to produce a protective effect. Oral treatment with a water-soluble HMG-CoA reductase inhibitor, RS, one week before as well as one week after the induction of RVH also effectively prevented CEC dysfunction and RVH. However, the extent of statin protective effects, were less dramatic as compared to that obtained from allicin-containing garlic, which probably reflected their diverse mode of action. Taken together, results of our studies demonstrate that the stimulation and preservation of coronary endothelial function represents a novel mechanism for the prevention of end-organ damages in cardiovascular disease. (Support by NIH NCCAM RO1 AT-001235)