Leptin reduces plasma ANP level via nitric oxide-dependent mechanism.
Leptin is a circulating adipocyte-derived hormone that influences blood pressure (BP) and metabolism. This study was designed to define the possible role of leptin in regulation of the atrial natriuretic peptide (ANP) system using acute and chronic experiments. Intravenous infusion of rat leptin (250 microg/kg injection plus 2 microg.kg(-1).min(-1) for 20 min) into Sprague-Dawley rats increased BP by 25 mmHg and decreased plasma level of ANP from 80.3 +/- 3.45 to 51.8 +/- 3.3 pg/ml. Reserpinization attenuated the rise in BP, but not the reduction of plasma ANP during leptin infusion. N(omega)-nitro-l-arginine methyl ester prevented the effects of leptin on the reduction of ANP level. In hyperleptinemic rats that received adenovirus containing rat leptin cDNA (AdCMV-leptin), BP increased during first 2 days and then recovered to control value. Plasma concentration of ANP and expression of ANP mRNA, but not of atrial ANP, in hyperleptinemic rats were lower than in the control groups on the first and second week after administration of AdCMV-leptin. These effects were not observed by the pretreatment with N(omega)-nitro-l-arginine methyl ester. No differences in renal function and ANP receptor density in the kidney were found between hyperleptinemic and control rats. Basal ANP secretion and isoproterenol-induced suppression of ANP secretion from isolated, perfused atria of hyperleptinemic rats were not different from those of other control groups. These data suggest that leptin inhibits ANP secretion indirectly through nitric oxide without changing basal or isoproterenol-induced ANP secretion.
Yuan
Kuichang
K
Department of Physiology, Chonbuk National University Medical School, Jeonju, Jeonbuk, 561-756, Korea.
Yu
Jiahua
J
Shah
Amin
A
Gao
Shan
S
Kim
Sun Young
SY
Kim
Sung Zoo
SZ
Park
Byung-Hyun
BH
Kim
Suhn Hee
SH
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000097:blood* / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002339:Carotid Arteries / Q000187:drug effects / Q000502:physiology; D006973:Hypertension / Q000097:blood / Q000139:chemically induced; D007545:Isoproterenol / Q000494:pharmacology; D007601:Jugular Veins / Q000187:drug effects / Q000502:physiology; D007668:Kidney / Q000187:drug effects / Q000502:physiology; D020738:Leptin / Q000097:blood / Q000494:pharmacology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D012333:RNA, Messenger / Q000097:blood / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012110:Reserpine / Q000494:pharmacology
D020738:Leptin; D012333:RNA, Messenger; D009569:Nitric Oxide; D009320:Atrial Natriuretic Factor; D012110:Reserpine; D007545:Isoproterenol; D019331:NG-Nitroarginine Methyl Ester