Role of leptin in obesity-related hypertension.

Obesity in humans causes hypertension, myocardial hypertrophy and coronary atherosclerosis, and increased cardiovascular morbidity and mortality that is thought to be related to sympathetic overactivity. Leptin is an adipocyte-derived hormone that acts in the hypothalamus to regulate appetite, energy expenditure and sympathetic nervous system outflow. One of the major mechanisms leading to the development of obesity-induced hypertension appears to be leptin-mediated sympatho-activation. Leptin adversely shifts the renal pressure-natriuresis curve, leading to relative sodium retention. Although obesity is generally associated with resistance to the anorexic and weight-reducing actions of leptin, our work has shown preservation of its sympatho-excitatory and pressor actions. This selective leptin resistance of obesity, coupled with hyperleptinaemia, may play a critical role in the cardiovascular complications of obesity. Increased information about leptin and its mechanisms of actions should help the development of safe and effective pharmacological treatments of obesity and obesity-related hypertension.