Excess Catecholamine Syndrome and insulin resistance
Exploration of causes leading to primary hypertension has become particularly relevant since centrally acting antihypertensive drugs have been developed that lower sympathetic outlow of the brain without exhibiting the well known side effects of early sympatholytic compounds. Parallel to the development of these selective imidazoline-I1 receptor agonists,  pathophysiological and psychological studies led to a further characterization of lifestyle factors that raise sympathetic outflow of the brain. In order to define these pathophysiological states, the term "Excess Catecholamine Syndrome" has been used (1). In ongoing studies, the concept is examined that catecholamines, that are in excess to the physical activity, induce various reactions in the body which eventually contribute to the development of hypertension, insulin resistance, hypertriglyceridemia and hyperuricemia.

The unfavorable effects of a raised sympathetic activity can be shown in normal persons after reflex stimulation of the sympathetic nervous system. In the experiment by Jamerson et al. (2), a supraphysiological dose of insulin was infused using the euglycemic hyperinsulinemic clamp technique. The increased insulin resulted - as expected - in a higher glucose utilisation. When a bilateral thigh compression was used to reduce the venous return to the heart, the glucose utilisation was impaired!

Various cardiopulmonary receptors monitor the venous filling of the heart and induce a rise in sympathetic outflow of the brain when venous return is reduced or the pressure development of the heart is depressed. As a consequence of the increased sympathetic activity, glucose utilization of the body is reduced. The study shows that reflex changes in sympathetic tone that are in the normal range of human physiological responses can induce insulin resistance. It appears that a raised sympathetic activity due to a high caloric intake has a similar action.

Figure adapted from: Jamerson KA, Julius S, Gudbrandsson T et al. Hypertension 1993;21:618-623.

Since insulin resistance precedes diabetes mellitus type-2, interventions which interfere with progression of insulin resistance are of utmost importance. Since moxonidine interferes with various adverse mechanisms that promote insulin resistance, it is not unexpected that it increases insulin sensitivity also in overweight or obese subjects. In our opinion, hypertension therapy should include an intervention that reduces insulin resistance, as is the case with moxonidine.

1. Rupp H: Excess catecholaminesyndrome. Pathophysiology and therapy. Ann N Y Acad Sci 1999;881:430-44. 
2. Jamerson KA, Julius S, Gudbrandsson T et al. Hypertension 1993;21:618-623.