Elevated circulating leptin levels in arterial hypertension: relationship to arteriovenous overflow and extraction of leptin

Leptin, a peptide hormone produced mainly in fat cells, appears to be important for the regulation of metabolism, insulin secretion/sensitivity and body weight. Recently, elevated plasma leptin levels have been reported in patients with arterial hypertension. Because a change in circulating leptin concentrations in such patients could be caused by altered rates of production or disposal, or both, the aim of the present study was to identify regions of leptin overflow into the bloodstream and of leptin extraction. Patients with arterial hypertension (n = 12) and normotensive controls (n = 20) were studied during catheterization with elective blood sampling from different vascular beds (artery, and renal, hepatic, iliac and cubital veins). Plasma leptin was determined by a radioimmunoassay. Patients with hypertension had significantly elevated levels of circulating leptin (12.8 ng/l, compared with 4.1 ng/l in the controls; P < 0.001), and this was also the case when adjusted for body mass index (BMI) [0.435 and 0.167 ng/l per unit BMI (kg/m(2)) respectively; P < 0.001]. Circulating leptin was directly related to arterial blood pressure (r = 0.38-0.62, P less than or equal to 0.05-0.005) and immunoreactive insulin (r = 0.51, P < 0.62), but not to plasma renin activity. A significant renal extraction ratio for leptin was seen in the hypertensive patients, but this was not significantly lower than that in the controls (0.09 compared with 0.16; P = 0.1). The hypertensive patients had a significantly higher hepatic venous/arterial leptin ratio than the controls (1.02 compared with 0.93; P < 0.02), and this ratio was correlated directly with the BMI (r = 0.38, P = 0.05) and immunoreactive insulin (r = 0.43, P < 0.05). In both hypertensive patients and controls there was a significant spillover of leptin into the iliac vein, but not into the cubital vein. In conclusion, the high concentration of circulating leptin in patients with arterial hypertension is probably caused by increased release of leptin from abdominal (especially mesenteric and omental) and gluteal adipose tissue stores, and renal extraction is slightly reduced. Leptin kinetics in arterial hypertension require further investigation.