title: Centrally administered insulin potentiates the pressor response to angiotensin II.
abstract: The aim of the present study was to determine if insulin can modulate the pressor response to angiotensin II at brain level in normotensive rats. Anaesthetized male rats were intracerebroventricularly infused with insulin (12 mU/h, n=15) or Ringer's solution as vehicle (n=15) for 2 h. Immediately, changes in mean arterial pressure (MAP) in response to an intracerebroventricular subpressor dose of angiotensin II (5 pmol, n=10) or vehicle (n=5) were measured for 10 min. Then, hypothalami were removed and Akt and ERK1/2 phosphorylation levels were determined. In other subset of animals, PD98059 (MAPK inhibitor) or vehicle were intracerebroventricularly administered previously to insulin perfusion for 2 h and changes in MAP in response to intracerebroventricular angiotensin II (5 pmol) injection were evaluated for 10 min (n=6 for each group). Angiotensin II did not modify MAP in vehicle pre-treated rats, but increased MAP in insulin pre-treated animals. Insulin significantly increased Akt phosphorylation, but no changes were observed after angiotensin II injection in vehicle-pretreated animals. Angiotensin II or insulin infusion increased in more than two fold phospho-ERK 1/2 hypothalamic levels. Animals that received insulin infusion followed by Ang II injection presented 4.5 higher values than those which received vehicle, and nearly twice than those who received Ang II without insulin pre-treatment. PD98059 administration abolished the blood pressure response exerted by angiotensin II in insulin pre-treated rats. In conclusion, centrally administered insulin potentiates the pressor effects to angiotensin II, suggesting a novel mechanism, possibly involving MAPK activation, by which insulin influences blood pressure control at central level.
authors.affiliation: Department of Anatomy and Histology, University of Buenos Aires, Junin 956, (C1113AAD), Buenos Aires, Argentina. marcos.mayer@gmail.com
authors.forename: Marcos A
authors.initials: MA
authors.lastname: Mayer
authors.forename: Jorge F
authors.initials: JF
authors.lastname: Giani
authors.forename: Christian
authors.initials: C
authors.lastname: Höcht
authors.forename: Ezequiel A
authors.initials: EA
authors.lastname: Silberman
authors.forename: Marina C
authors.initials: MC
authors.lastname: Muñoz
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Taira
authors.forename: Fernando P
authors.initials: FP
authors.lastname: Dominici
authors.forename: Ana M
authors.initials: AM
authors.lastname: Puyó
authors.forename: Belisario E
authors.initials: BE
authors.lastname: Fernández
mesh_terms: D000804:Angiotensin II / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D005419:Flavonoids / Q000494:pharmacology; D007328:Insulin / Q000008:administration & dosage* / Q000494:pharmacology*; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D005419:Flavonoids; D007328:Insulin; D000804:Angiotensin II; D020928:Mitogen-Activated Protein Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one