Leptin acts in the central nervous system to produce dose-dependent changes in arterial pressure.
Systemic leptin increases energy expenditure through sympathetic mechanisms, decreases appetite, and increases arterial pressure. We tested the hypothesis that the pressor action of leptin is mediated by the central nervous system. The interaction of dietary salt with leptin was also studied. Leptin was infused for 2 to 4 weeks into the third cerebral ventricle of Sprague-Dawley rats. Arterial pressure was measured by radiotelemetry. To control for the effects of leptin on body weight, vehicle-treated rats were pair-fed to the leptin group. Intracerebroventricular infusion of leptin at 200 ng/h in salt-depleted rats caused a reduction in food intake, weight loss, tachycardia, and decreased arterial pressure. Leptin at 1000 ng/h caused further reduction in food intake, weight loss, and tachycardia and prevented the hypotensive effect of weight loss observed in pair-fed, vehicle-treated animals. Intracerebroventricular leptin at 1000 ng/h in high-salt-fed rats also caused a sustained pressor response (+3+/-1 mm Hg), but high-salt intake did not potentiate the pressor effect of leptin. Intracerebroventricular leptin potentiated the pressor effect of air-jet stress. Intravenous administration of the same dose of leptin (1000 ng/h) did not change weight or arterial pressure, suggesting a direct central nervous system action. In contrast, a high dose of intravenous leptin (18 000 ng/h) caused weight loss and prevented the depressor effect of weight loss. In conclusion, this study demonstrates that high-dose leptin increases arterial pressure and heart rate through central neural mechanisms but leptin does not enhance salt sensitivity of arterial pressure. Leptin appears to oppose the depressor effect of weight loss.
Specialized Center of Research in Hypertension Genetics, the Cardiovascular Center and Department of Internal Medicine, The University of Iowa, and Veterans Affairs Medical Center, Iowa City, Iowa 52242, USA.
M L
ML
Correia
D A
DA
Morgan
W I
WI
Sivitz
A L
AL
Mark
W G
WG
Haynes
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002490:Central Nervous System / Q000187:drug effects* / Q000502:physiology; D004039:Diet, Sodium-Restricted; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D007276:Injections, Intraventricular; D020738:Leptin / Q000097:blood / Q000134:cerebrospinal fluid / Q000494:pharmacology* / Q000633:toxicity; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012965:Sodium Chloride / Q000008:administration & dosage; D013312:Stress, Physiological / Q000503:physiopathology; D013610:Tachycardia / Q000139:chemically induced; D013686:Telemetry
D020738:Leptin; D012965:Sodium Chloride