Figure 7.

Possible mechanisms for the leptin-induced BP elevation in transgenic skinny mice (a) and KKAy mice (b). In transgenic skinny mice (a), leptin is oversecreted ectopically from the liver into the circulation, which causes the skinny phenotype with decreased food intake and a significant BP elevation with increased catecholamine production. They are hypoinsulinemic with hypersensitivity to insulin (28). Decrease in food intake is reversed by SHU9119, whereas BP elevation is not abolished by SHU9119 but by bunazosin, propranolol, and hexamethonium. In KKAy mice (b), leptin is oversecreted from the adipose tissue into the circulation, which causes significant BP elevation with increased catecholamine production, although they are hyperphagic owing to the antagonism of hypothalamic melanocortin system by the agouti protein. They are hyperinsulinemic with marked resistance to insulin (30, 31). CA, catecholamine.