As the world faces an
obesity "epidemic," the mechanisms by which
overweight is translated into
insulin resistance,
hypertension, and diabetes need to be better understood. Although the processes of transition remain uncertain, overactivity of the sympathetic nervous system appears pivotal. In
obesity, there is stimulation of sympathetic outflow to the kidneys, evident in increased rates of spillover of
noradrenaline into the renal veins, and to skeletal muscle vasculature, demonstrated with microneurography. The cause is unclear, but possibly involves the stimulatory action of
leptin released from adipose tissue, or from within the brain, for which there is recent evidence in human
obesity. The high renal sympathetic tone contributes to
hypertension development by stimulating
renin secretion and through promoting renal tubular reabsorption of
sodium. Neurally mediated skeletal muscle vasoconstriction reduces
glucose delivery and uptake in muscle. Impairment of
glucose uptake by skeletal muscle is a hallmark of
insulin resistance syndromes. Pharmacologic sympathetic nervous suppression within the central nervous system with
imidazoline receptor-binding agents such as
rilmenidine is a logical therapeutic approach for lowering blood pressure (BP) in patients with
essential hypertension, in whom sympathetic activity is often increased. In addition, drugs of this class appear to have the capacity to favorably modify
insulin sensitivity, which has particular relevance in the treatment of hypertensive diabetic patients. In the
hypertension accompanying maturity onset
obesity, with recent recommendations from advisory bodies setting lower goal BP, and with these lower targets often being reached only with combinations of
antihypertensive agents, it is advisable that all drugs used in combination
therapy have a favorable or at least a neutral effect on
insulin resistance.