Structural and functional evidence supporting a role for leptin in central neural pathways influencing blood pressure in rats

Leptin, a peptide hormone normally associated with body weight homeostasis, is implicated in the generation of obesity-induced hypertension. Administration of leptin increases sympathetic nerve activity and blood pressure; however, the neural circuity involved in this pressor effect is not clearly defined. In this review we describe experiments in which pseudorabies virus was injected into the heart, kidney and the vasculature within skeletal muscle to reveal the distribution of neurones in the hypothalamus that project to these cardiovascular tissues. This distribution is compared to the well-documented distribution of leptin receptors. Finally we discuss microinjection studies designed to examine the effect of leptin, in these regions, on sympathetic nerve discharge and arterial blood pressure. Leptin injected directly into the ventromedial hypothalamus, arcuate nucleus and lateral hypothalamic area (particularly the perifornical area) increased lumbar sympathetic nerve activity. In addition, microinjection into the ventromedial hypothalamus and parvocellular paraventricular nucleus increased blood pressure. Our results demonstrate a discrete set of hypothalamic pathways that may underlie the involvement of leptin in obesity-induced hypertension.