title: Leptin regulates ACE activity in mice.
abstract: 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.
authors.affiliation: Department of Biophysics, Escola Paulista de Medicina, Federal University of São Paulo, 04023-062 São Paulo, SP, Brazil.
authors.forename: Aline Mourao
authors.initials: AM
authors.lastname: Hilzendeger
authors.forename: Rafael Leite
authors.initials: RL
authors.lastname: Morais
authors.forename: Mihail
authors.initials: M
authors.lastname: Todiras
authors.forename: Ralph
authors.initials: R
authors.lastname: Plehm
authors.forename: Andrey
authors.initials: A
authors.lastname: da Costa Goncalves
authors.forename: Fatimunnisa
authors.initials: F
authors.lastname: Qadri
authors.forename: Ronaldo Carvalho
authors.initials: RC
authors.lastname: Araujo
authors.forename: Volkmar
authors.initials: V
authors.lastname: Gross
authors.forename: Clovis Ryuichi
authors.initials: CR
authors.lastname: Nakaie
authors.forename: Dulce Elena
authors.initials: DE
authors.lastname: Casarini
authors.forename: Adriana Karaoglanovic
authors.initials: AK
authors.lastname: Carmona
authors.forename: Michael
authors.initials: M
authors.lastname: Bader
authors.forename: João Bosco
authors.initials: JB
authors.lastname: Pesquero
mesh_terms: 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
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D020738:Leptin; D012333:RNA, Messenger; D004656:Enalapril; D007703:Peptidyl-Dipeptidase A