Leptin regulates ACE activity in mice.
Leptin is a hormone related to metabolism. It also influences blood pressure, but the mechanisms triggered in this process are not yet elucidated. Angiotensin-I converting enzyme (ACE) regulates cardiovascular functions and recently has been associated with metabolism control and obesity. Here, we used ob/ob mice, a model lacking leptin, to answer the question whether ACE and leptin could interact to influence blood pressure, thereby linking the renin-angiotensin system and obesity. These mice are obese and diabetic but have normal 24 h mean arterial pressure. Our results show that plasma and lung ACE activities as well as ACE mRNA expression were significantly decreased in ob/ob mice. In agreement with these findings, the hypotensive effect produced by enalapril administration was attenuated in the obese mice. Plasma renin, angiotensinogen, angiotensin I, bradykinin, and angiotensin 1-7 were increased, whereas plasma angiotensin II concentration was unchanged in obese mice. Chronic infusion of leptin increased renin activity and angiotensin II concentration in both groups and increased ACE activity in ob/ob mice. Acute leptin infusion restored ACE activity in leptin-deficient mice. Moreover, the effect of an ACE inhibitor on blood pressure was not changed in ob/+ mice during leptin treatment but increased four times in obese mice. In summary, our findings show that the renin-angiotensin system is altered in ob/ob mice, with markedly reduced ACE activity, which suggests a possible connection between the renin-angiotensin system and leptin. These results point to an important interplay between the angiotensinergic and the leptinergic systems, which may play a role in the pathogenesis of obesity, hypertension, and metabolic syndrome.
Hilzendeger
Aline Mourao
AM
Department of Biophysics, Escola Paulista de Medicina, Federal University of São Paulo, 04023-062 São Paulo, SP, Brazil.
Morais
Rafael Leite
RL
Todiras
Mihail
M
Plehm
Ralph
R
da Costa Goncalves
Andrey
A
Qadri
Fatimunnisa
F
Araujo
Ronaldo Carvalho
RC
Gross
Volkmar
V
Nakaie
Clovis Ryuichi
CR
Casarini
Dulce Elena
DE
Carmona
Adriana Karaoglanovic
AK
Bader
Michael
M
Pesquero
João Bosco
JB
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D004656:Enalapril / Q000494:pharmacology; D020738:Leptin / Q000378:metabolism*; D008297:Male; D051379:Mice; D008820:Mice, Obese; D008822:Mice, Transgenic; D009765:Obesity / Q000378:metabolism; D007703:Peptidyl-Dipeptidase A / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000502:physiology
D000806:Angiotensin-Converting Enzyme Inhibitors; D020738:Leptin; D012333:RNA, Messenger; D004656:Enalapril; D007703:Peptidyl-Dipeptidase A