Role of nitric oxide and endothelium-derived hyperpolarizing factor (EDHF) in the regulation of blood pressure by leptin in lean and obese rats.
We investigated the role of nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF) in hemodynamic action of leptin. The effect of leptin (1 mg/kg i.p.) on systolic blood pressure (SBP) was examined in lean rats and in rats made obese by feeding highly palatable diet for either 1 or 3 months. Separate groups received NO synthase inhibitor, L-NAME, or EDHF inhibitors, the mixture of apamin+charybdotoxin or sulfaphenazole, before leptin administration. Leptin increased NO production, as evidenced by increase in plasma and urinary NO metabolites and cyclic GMP. This effect was impaired in both obese groups. In lean rats either leptin or EDHF inhibitors had no effect on blood pressure. L-NAME increased blood pressure in lean animals and this effect was prevented by leptin. However, when leptin was administered to animals pretreated with both L-NAME and EDHF inhibitors, blood pressure increased even more than after L-NAME alone. In the 1-month obese group leptin had no effect on SBP, however, pressor effect of leptin was observed in animals pretreated with EDHF inhibitors. In the 3-month obese group leptin alone increased SBP, and EDHF inhibitors did not augment its pressor effect. The results suggest that leptin may stimulate EDHF when NO becomes deficient, e.g. after NOS blockade or in short-term obesity. Although the effect of leptin on NO production is impaired in the 1-month obese group, BP does not increase, probably because EDHF compensates for NO deficiency. In contrast, leptin increases BP in 3-month obesity because its effect on EDHF is also attenuated.
Bełtowski
Jerzy
J
Department of Pathophysiology, Medical University, ul. Jaczewskiego 8, 20-090 Lublin, Poland. jerzy.beltowski@am.lublin.pl
Wójcicka
Grazyna
G
Jamroz-Wiśniewska
Anna
A
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000818:Animals; D001685:Biological Factors / Q000502:physiology*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D001835:Body Weight / Q000502:physiology; D006152:Cyclic GMP / Q000378:metabolism; D004032:Diet; D007202:Indicators and Reagents; D028421:Isoprostanes / Q000097:blood; D020738:Leptin / Q000494:pharmacology*; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D009765:Obesity / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar
D001685:Biological Factors; D007202:Indicators and Reagents; D028421:Isoprostanes; D020738:Leptin; C067410:endothelium-dependent hyperpolarization factor; D009569:Nitric Oxide; D015121:6-Ketoprostaglandin F1 alpha; D006152:Cyclic GMP