title: Increased blood pressure and water intake in transgenic mice expressing rat tonin in the brain.
abstract: Tonin is a serine proteinase of the kallikrein family that can produce angiotensin II directly from angiotensinogen. To clarify the importance of this enzyme for central nervous control of the cardiovascular system, we generated transgenic mice, TGM(rTon), that express rat tonin in astrocytes. These mice present high levels of tonin mRNA and activity specifically in the brain. As a consequence, TGM(rTon) develop increased blood pressure and water intake. Lisinopril, an ACE inhibitor, is less hypotensive for transgenic mice than for control animals. The AT(1) receptor antagonist candesartan equally lowers blood pressure in transgenic and in control mice. Plasma angiotensin II, but not angiotensin I, is increased in TGM(rTon) compared to the wild type, suggesting release of the peptide from the brain into the circulation. However, AT(1) receptors are desensitized in this transgenic model, as demonstrated by a blunted pressor response to intravenous application of angiotensin II. In conclusion, tonin in the brain may represent an alternative pathway for angiotensin II generation with effects on the cardiovascular system.
authors.affiliation: Max-Delbrück Center for Molecular Medicine, Berlin-Buch, Germany.
authors.forename: Cibele C
authors.initials: CC
authors.lastname: Cardoso
authors.forename: Natalia
authors.initials: N
authors.lastname: Alenina
authors.forename: Anderson J
authors.initials: AJ
authors.lastname: Ferreira
authors.forename: Fatimunnisa
authors.initials: F
authors.lastname: Qadri
authors.forename: Mércia P
authors.initials: MP
authors.lastname: Lima
authors.forename: Volkmar
authors.initials: V
authors.lastname: Gross
authors.forename: Mihail
authors.initials: M
authors.lastname: Todiras
authors.forename: João B
authors.initials: JB
authors.lastname: Pesquero
authors.forename: Jorge L
authors.initials: JL
authors.lastname: Pesquero
authors.forename: Michael
authors.initials: M
authors.lastname: Bader
mesh_terms: D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure / Q000235:genetics*; D001921:Brain / Q000378:metabolism*; D004326:Drinking / Q000235:genetics*; D015870:Gene Expression; D007668:Kidney / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D051381:Rats; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000235:genetics; D020840:Tissue Kallikreins / Q000235:genetics*
chemical_list: D044140:Receptor, Angiotensin, Type 1; D000804:Angiotensin II; C117017:tonin; D020840:Tissue Kallikreins