Cardiovascular and sympathetic effects of disrupting tyrosine 985 of the XXXX .

@entity19 @entity18070 @entity8
Leptin acts in the brain to regulate food intake and energy expenditure. Leptin also increases renal sympathetic nerve activity and arterial pressure. The divergent signaling capacities of the @entity18070 (ObRb) mediate the stimulation of various intracellular pathways that are important for leptin control of physiological processes. We evaluated the cardiovascular and sympathetic consequences of disrupting the signal emanating from tyrosine985 of ObRb. For this, we used @entity18070 ) (l/l) @entity19 , which carry a loss of function mutation replacing tyrosine985 of ObRb with leucine. Body weight of l/l @entity19 was not significantly different from wild-type controls. In contrast, radiotelemetry measurements revealed that the l/l @entity19 had higher arterial pressure and heart rate as compared with controls. Ganglionic blockade caused a greater arterial pressure fall in the l/l @entity19 relative to controls. In addition, leptin treatment induced a larger increase in arterial pressure and heart rate in the l/l versus wild-type @entity19 . Finally, we compared the response of renal and brown adipose tissue sympathetic nerve activity to intracerebroventricular injection of leptin (2  g) between l/l and control @entity19 . Leptin-induced @entity8 was greater in l/l @entity19 relative to controls. In contrast, the brown adipose tissue sympathetic nerve activity response to leptin was attenuated in the l/l @entity19 relative to controls. These data indicate that selective loss of @entity18070 signaling emanating from tyrosine985 enhances the cardiovascular and renal sympathetic effects of leptin. These findings provide important insight into the molecular mechanisms underlying leptin's effects on the sympathetic cardiovascular function and arterial pressure.
