EXCESS CATECHOLAMINES AND THE METABOLIC SYNDROME - SHOULD CENTRAL IMIDAZOLINE RECEPTORS BE A THERAPEUTIC TARGET

A sympathetic overactivity plays a major role in the pathogenesis of c ardiovascular diseases in Westernized affluent societies. Of importanc e is an increased caloric intake and psychosocial stress which are ass ociated with a raised central sympathetic outflow and unfavourable cha nges in metabolic parameters. Normalization of central sympathetic out flow could thus be a major therapeutic target. The newly developed ant ihypertensive drugs moxonidine and rilmenidine reduce the excitatory a ctivity of neurons of the rostral ventrolateral medulla (RVLM) via bin ding to imidazoline receptors. Using radio telemetry, it is shown that , in contrast to the first generation centrally acting drug clonidine, moxonidine did not result in rebound of blood pressure after drug wit hdrawal in rats with spontaneous hypertension. In accordance, moxonidi ne is characterized by a low affinity for a-adrenoceptors and exhibits few side-effects. It is proposed that normalization of central sympat hetic outflow represents a causal approach for improving crucial featu res of the metabolic syndrome.