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 cardiovascular diseases in Westernized affluent societies. Of importance is an increased caloric intake and psychosocial stress which are associated with a raised central sympathetic outflow and unfavourable changes in metabolic parameters. Normalization of central sympathetic outflow could thus be a major therapeutic target. The newly developed antihypertensive drugs moxonidine and rilmenidine reduce the excitatory activity of neurons of the rostral ventrolateral medulla (RVLM) via binding 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 withdrawal in rats with spontaneous hypertension. In accordance, moxonidine is characterized by a low affinity for alpha-adrenoceptors and exhibits few side-effects. It is proposed that normalization of central sympathetic outflow represents a causal approach for improving crucial features of the metabolic syndrome.