Hemodynamic changes after acute and long-term combined alpha--beta-adrenoceptor blockade with labetalol as compared...

The hemodynamic pattern in hypertension varies according to the age of the subject and the stage of the hypertensive disorder. In the early stage, both cardiac output and systemic vascular resistance tend to be elevated. Already at that stage, mild degrees of left ventricular function disturbance can be detected. Advanced stages are characterized by a hypokinetic type of circulation with subnormal cardiac output and considerably increased systemic vascular resistance. Both cardioselective and nonselective beta-receptor antagonists lower cardiac output and tend to raise systemic vascular resistance. Even left ventricular filling pressures tend to be higher. While these effects are most distinct in the acute experiment, cardiac output remains always depressed and systemic vascular resistance stabilizes often at a higher level, compared with pretreatment values, even during long-term therapy. The antihypertensive action of beta-receptor blockers appears to be mainly due to the reduction of cardiac output. Combined alpha--beta-adrenergic blockade lowers blood pressure predominantly by alpha-adrenoceptor-mediated reduction of systemic vascular resistance both when induced acutely and during long-term administration. Owing to its beta-adrenoceptor blocking component, the increase of cardiac output is abolished: cardiac output is maintained at pretreatment levels, as is left ventricular filling pressure. Since a well-balanced blockade of both alpha- and beta-adrenergic receptors counteracts the hemodynamic changes occurring in the course of hypertension and tends to restore cardiovascular dynamics towards normal, combined alpha--beta-adrenoceptor blockade appears to be one of the most logical and rational therapeutical approaches to hypertension.