Effects of central leptin administration on blood pressure in normotensive rats.

We tested the hypothesis that intracerebroventricular (i.c.v.) administration of leptin would increase mean arterial pressure (MAP) in ad libitum (AL) fed and food deprived (FD) normotensive rats. Male Sprague-Dawley rats were chronically instrumented with a guide cannula directed at the lateral ventricle and a carotid arterial catheter. Following recovery from surgery, the MAP and heart rate (HR) response to i.c.v. administration of vehicle (5 microl saline over 1 min) or leptin (0.3 microg or 3.0 microg in 5 microl saline) were determined in conscious, unrestrained AL fed (n=7-10) and 48-h FD (n=5-10) rats. Food deprivation significantly reduced MAP (AL=116+/-3; FD=104+/-3 mmHg; P < 0.01) without altering HR. In AL rats, high dose leptin (3.0 microg, i.c.v.) produced a significant increase in MAP when maximal responses were evaluated (9+/-2 mmHg; P < 0.05), but did not significantly alter MAP and HR over time during the 90 min measurement period. In FD rats, low dose leptin (0.3 microg, i.c.v.) produced significant elevations in MAP (7+/-3 mmHg) after a latency of 60 min, while high dose leptin (3.0 microg, i.c.v.) produced an increase in MAP within the first 10 min (10+/-3 mmHg) followed by an additional increase 1 h after injection (6+/-2 mmHg). Leptin administration also produced delayed increases in HR in FD rats (0.3 microg, 34+/-5 b.p.m.; 3.0 microg, 57+/-10 b.p.m). These results indicate that leptin may modulate cardiovascular function through central mechanisms and may do so to a greater extent in food deprived animals.