OVERVIEW OF ALPHA(1)-ADRENOCEPTOR ANTAGONISM AND RECENT ADVANCES IN HYPERTENSIVE THERAPY

alpha(1)-Receptor antagonists are potent blood pressure lowering drugs , although the use of alpha(1)-receptor antagonists by physicians in t he treatment of hypertension has been somewhat reserved. The major con cern are symptoms of orthostatic dysregulation and syncopes. However, reports on a long-acting second generation of alpha 1-adrenoceptor ant agonists demonstrate that orthostatic dysregulation is not more freque nt in patients treated with these compounds as compared to other antih ypertensive drugs. Since blood pressure readings at patients' work sit es are of greater prognostic value for the fatal events of cardiovascu lar disease, the impact of any antihypertensive agent on cardiovascula r reactivity during stress becomes most important. Long-acting alpha-a drenoceptor antagonists control blood pressure during stressful events , ie, stimulation of the sympathetic nervous system without altering t he physiologic hemodynamic profile. Sustained elevated blood pressure imposes a burden on the cardiovascular system, in particular on arteri es, arterial resistance vessels, the cerebrovascular circulation, the kidneys, and the heart. Since the extent of target organ damage is res ponsible for the impaired prognosis of the hypertensive patient, regre ssion of early hypertensive organ alterations is a most desirable ther apeutic goal. In a series of clinical trials we found that alpha(1)-re ceptor antagonists reduced left ventricular hypertrophy (an independen t risk factor for cardiovascular mortality and morbidity), lowered tot al peripheral resistance (related to vascular resistance vessels), imp roved glomerular filtration rate, and had no effect or improved lipid metabolism, glucose tolerance, and insulin resistance. Hence, alpha(1) -adrenoceptor antagonists emerged as attractive agents for antihyperte nsive therapy.