Centrally administered insulin potentiates the pressor response to angiotensin II

M. A. MAYER; J. F. GIANI; C HÖCHT; E. A. SILBERMAN; M. C. MUÑOZ; C. TAIRA; F. P. DOMINICI; A. M. PUYÓ; B.E. FERNÁNDEZ

REGULATORY PEPTIDES

ELSEVIER SCIENCE BV

Año: 2010 vol. 163 p. 157 - 161

0167-0115

The aim of the present study was to determine if insulin can modulate the pressor response to angiotensin IIat brain level in normotensive rats.Anaesthetized male rats were intracerebroventricularly infused with insulin (12 mU/h, n=15) or Ringer’ssolution as vehicle (n=15) for 2h. Immediately, changes in mean arterial pressure (MAP) in response to anintracerebroventricular subpressor dose of angiotensin II (5 pmol, n=10) or vehicle (n=5) were measuredfor 10min. Then, hypothalami were removed and Akt and ERK1/2 phosphorylation levels were determined.In other subset of animals, PD98059 (MAPK inhibitor) or vehicle were intracerebroventricularlyadministered previously to insulin perfusion for 2 h and changes in MAP in response to intracerebroventricularangiotensin II (5 pmol) injection were evaluated for 10min (n=6 for each group).Angiotensin II did not modify MAP in vehicle pre-treated rats, but increased MAP in insulin pre-treatedanimals. Insulin significantly increased Akt phosphorylation, but no changes were observed after angiotensinII injection in vehicle-pretreated animals. Angiotensin II or insulin infusion increased in more than two foldphospho-ERK 1/2 hypothalamic levels. Animals that received insulin infusion followed by Ang II injectionpresented 4.5 higher values than those which received vehicle, and nearly twice than those who receivedAng II without insulin pre-treatment. PD98059 administration abolished the blood pressure responseexerted by angiotensin II in insulin pre-treated rats.In conclusion, centrally administered insulin potentiates the pressor effects to angiotensin II, suggesting anovel mechanism, possibly involving MAPK activation, by which insulin influences blood pressure control atcentral level.