Overview of α1-Adrenoceptor Antagonism and Recent Advances in Hypertensive Therapy

α1-Receptor antagonists are potent blood pressure lowering drugs, although the use of α1-receptor antagonists by physicians in the treatment of hypertension has been somewhat reserved. The major concern are symptoms of orthostatic dysregulation and syncopes. However, reports on a long-acting second generation of α1-adrenoceptor antagonists demonstrate that orthostatic dysregulation is not more frequent in patients treated with these compounds as compared to other antihypertensive drugs. Since blood pressure readings at patientsʹ work sites are of greater prognostic value for the fatal events of cardiovascular disease, the impact of any antihypertensive agent on cardiovascular reactivity during stress becomes most important. Long-acting α-adrenoceptor antagonists control blood pressure during stressful events, ie, stimulation of the sympathetic nervous system without altering the physiologic hemodynamic profile. Sustained elevated blood pressure imposes a burden on the cardiovascular system, in particular on arteries, arterial resistance vessels, the cerebrosvascular circulation, the kidneys, and the heart. Since the extent of target organ damage is responsible for the impaired prognosis of the hypertensive patient, regression of early hypertensive organ alterations is a most desirable therapeutic goal. In a series of clinical trials we found that α1-receptor antagonists reduced left ventricular hypertrophy (an independent risk factor for cardiovascular mortality and morbidity), lowered total peripheral resistance (related to vascular resistance vessels), improved glomerular filtration rate, and had no effect or improved lipid metabolism, glucose tolerance, and insulin resistance. Hence, α1-adrenoceptor antagonists emerged as attractive agents for antihypertensive therapy. Am J Hypertens 1996;9:139S–149S