Effects of chronic nitric oxide inhibition on the renal excretory response to leptin.
OBJECTIVE
Previous investigations have demonstrated that leptin promotes natriuresis with a renal tubular effect. However, the mechanisms involved in this response are unclear. The present study was designed to examine the hypothesis that the natriuretic response to leptin in normotensive Sprague-Dawley rats is regulated by nitric oxide (NO).


METHODS
The hemodynamic and renal excretory effects of intravenous bolus administration of pharmacological doses of synthetic murine leptin were examined in groups of control Sprague-Dawley rats (n = 8), Sprague-Dawley rats treated for 4 days with the NO synthase inhibitor Nomega-nitro-L-arginine methyl ester (L-NAME) (n = 8), and Sprague-Dawley rats treated for 4 days with L-NAME followed by acute treatment with sodium nitroprusside (n = 8).


RESULTS
In the control group (n = 8), an intravenous bolus of leptin, 400 microg/kg body weight, increased urinary sodium excretion 4- to 6-fold. In the Sprague-Dawley rats chronically administered l-NAME (n = 8), an intravenous bolus of 400 microg/kg of leptin did not increase sodium excretion. Acute sodium nitroprusside infusion to Sprague-Dawley rats chronically treated with L-NAME (n = 8) was associated with partial restoration of the sodium excretory response to leptin administration.


CONCLUSIONS
Collectively, these results are interpreted to suggest that the natriuretic and diuretic responses to leptin observed in the Sprague-Dawley rat require a functional NO system.
Villarreal
Daniel
D
Department of Internal Medicine, SUNY Upstate Medical University, Syracuse, NY 13210, USA. Villarrd@upstate.ed
Reams
Garry
G
Samar
Huma
H
Spear
Robert
R
Freeman
Ronald H
RH
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D020738:Leptin / Q000494:pharmacology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009318:Natriuresis / Q000187:drug effects* / Q000502:physiology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000502:physiology; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000652:urine
D004791:Enzyme Inhibitors; D020738:Leptin; D020030:Nitric Oxide Donors; D009599:Nitroprusside; D009569:Nitric Oxide; D012964:Sodium; D019331:NG-Nitroarginine Methyl Ester