The effect of nebivolol treatment to the endothelial dysfunction and exercise induced ischemia in patients with cardiac syndrome X

Normal-appearing coronary arteries are found in 10-30% of patients who undergocoronary angiography because of angina. The clinical entity is called cardiac syndrome X, inwhich patients present with angina-like pain on effort, ST segment depression on an exercisestress test and normal coronary arteries at angiography, in the absence of any other cardiacdiseases or systemic diseases (e.g. hypertension, diabetes) known to influence vascularfunction. The cause of myocardial ischemia and chest pain in patients with cardiacsyndrome X has been explained by mechanisms including impaired coronary flow reservedue to endothelial dysfunction. Nitrates, beta-blockers, calcium channel blockers, andtricyclics are conventionally have been used in treatment of CSX due to potentially alterpain perception. Nebivolol is a highly selective b1-adrenergic receptor antagonist that alsopossesses vasodilator properties that are attributed to endothelium derived NO. Our studysought to determine whether nebivolol effects coronary endothelial function and exerciseinduced ischemia in patients with cardiac syndrome X. After a 2-weeks washout period, 38patients with syndrome X were randomized to receive either nebivolol 5 mg one daily (n =19) or metoprolol (n = 19) in a single-blind design for 12 weeks. Four patients werewithdrawn from the study for several different reasons. All patients underwent standardexercise stress test using the modified Bruce protocol on two occasions: beforerandomization and at the end of 12 week. From each subjects, a fasting blood sample wasobtained from the antecubital fossa vein in the morning hours before randomization and atthe end of 12 week. Before drug treatment, plasma level of NOx and L-arginine were lowerthan patients with syndrome-X compared to the control?s. Nevertheless, plasma ADMAlevel was increased in the patient group. Also, the levels of plasma NOx, ADMA, and L-43arginine were comparable between two treatment groups before treatment. After 12 weeksof drug therapy, the patients taking nebivolol had increased levels of plasma NOx, plasmaL-arginine and decresed levels of plasma ADMA compared to those of the patients takingmetoprolol. At the end of 12 weeks, the patients who received nebivolol, both exerciseduration to 1-mm ST depression and total exercise duration increased significantly aftertreatment. Although such parameters were slightly increased in metoprolol recipients, thisdifference did not reach statistical significance. We have found that the circulatingendothelial function parameters ( plasma ADMA, L-arginine, NOx levels) were impaired inpatients with CSX. Taking with nebivolol treatment, these parameters were ameliorated withbetter exercise stress test parameters when compared to metoprolol treatment. Last but notleast, we believe that further studies are needed to evaluate the effects of nebivolol treatmenton long-term clinical outcomes in patients with CSX.