Rationale for combined alpha-beta-adrenoceptor blockade: haemodynamic considerations

Increased peripheral vascular resistance is the cause of elevated blood pressure in most forms of systemic hypertension. Both structural changes in response to increased wall stress and functional alterations in vascular smooth muscle itself appear to contribute to the elevated resistance. As mediators of the vasoconstrictor responses, alpha-adrenoceptors apparently play an important if not predominant role in the initiation and/or maintenance of high resistance and pressure. In contrast to beta-receptor blockade alone, combined alpha-beta-receptor blockade lowers blood pressure predominantly by alpha-receptor-mediated reduction of the systemic vascular resistance, both when induced acutely and, in particular, during long-term administration. Cardiac output is maintained at pretreatment level, as is left ventricular filling pressure. Since a well-balanced blockade of both alpha- and beta-receptors counteracts the pathophysiological changes causing and/or maintaining hypertension and tends to restore cardiovascular dynamics towards normal, combined alpha-beta-receptor blockade appears at present to be one of the most logical and rational therapeutic approaches to hypertension.