Pivotal role of nitric oxide in the control of blood pressure after leptin administration.
Leptin administration has been shown to increase renal, adrenal, and lumbar sympathetic nerve activity. However, this generalized sympathoexcitatory activity is not always followed by an increase in arterial pressure. The present study tested the hypothesis that leptin induces a release of nitric oxide (NO) that opposes the pressor effect of sympathoexcitation. The effect of intravenous administration of leptin (10, 100, and 1,000 microg/kg body wt) or vehicle on blood pressure (BP), heart rate (HR), and serum nitrite/nitrate concentrations of anesthetized Wistar rats was examined. At 90 min after injection, the three leptin doses tested increased serum NO concentrations 20.5, 33.1, and 89.5%, respectively (P < 0.001 vs. baseline). The effect of leptin on NO concentrations was significantly dose-dependent on linear trend testing (P = 0.0001). In contrast, leptin did not change serum nitrite/nitrate concentrations of fa/fa rats. Leptin administration to Wistar rats under NO synthesis inhibition (N(omega)-nitro-L-arginine methyl ester [L-NAME]) produced a statistically significant increase (P < 0.05) in both systolic BP and mean arterial pressure as well as in HR (P < 0.01). Injection of leptin into rats with pharmacologically induced ganglionic blockade (chlorisondamine) was followed by a decrease in BP and HR to values significantly lower (P < 0.01) than those observed with chlorisondamine treatment alone. The leptin-induced hypotension observed in the setting of ganglionic blockade was blocked by L-NAME. These findings raise the possibility that the leptin-induced release of NO may contribute to the homeostasis of BP.
Frühbeck
G
G
Department of Endocrinology, Clínica Universitaria de Navarra, University of Navarra, Pamplona, Spain. gfruhbeck@unav.es
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002714:Chlorisondamine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005730:Ganglionic Blockers / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects; D020738:Leptin; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009573:Nitrites / Q000097:blood; D011506:Proteins / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011924:Rats, Zucker; D012016:Reference Values
D004791:Enzyme Inhibitors; D005730:Ganglionic Blockers; D020738:Leptin; D009566:Nitrates; D009573:Nitrites; D011506:Proteins; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D002714:Chlorisondamine; D019331:NG-Nitroarginine Methyl Ester