Besides its role in body weight control leptin may also act as a vasoactive hormone. This study was designed to investigate whether leptin modifies angiotensin II (ANG II)-induced vascular responses. The expression of functional leptin receptors (OB-Rb) was detected in vascular smooth muscle cells (VSMCs) from adult Wistar rats by RT-PCR. Immunocytochemistry and Western blot analysis further showed the expression of OB-R protein in VSMCs. The ANG II (10(-7) mol/liter)-induced increase in intracellular Ca(2+) was blocked (P < 0.01) by leptin (10(-8) mol/liter). Moreover, in calcium-free buffer leptin was able to inhibit 65% of the ANG II-induced calcium release from intracellular stores. In endothelium-denuded aortic rings from adult Wistar rats no effect of leptin on basal tension was observed. However, the ANG II-induced isometric contraction was reduced (P < 0.05) by leptin (10(-8) mol/liter). The experiments were also performed in age- and sex-matched Zucker rats, in which no effect of leptin on ANG II-induced calcium increase and vasoconstriction was observed. It is concluded that leptin blocks the vasoconstrictor action of ANG II and inhibits the ANG II-induced increase in intracellular Ca(2+) in VSMCs through OB-Rb. These findings provide new insight into the physiological effects of leptin on blood pressure regulation.