“ENDOTHELIUM-DEPENDENT RESPONSE TO ANGIOTENSIN II AND NORADRENALINE IN RABBITS FEED ON A HIGH FAT DIET

FABRICIO SCACCHI; LILIANA SIERRA; RAMIRO GUERRERO; SILVIA SAAD DE SCHOOS; MARÍA PERAL DE BRUNO; SUSANA JEREZ

Rosario

Congreso; LXI Reunión Anual de la Sociedad Argentina de Farmacología Vascular Experimental (SAFE); 2009

Sociedad Argentina de Farmacología Vascular Experimental (SAFE)

The aim of this work was to study the role of endothelium in the contractile response to angiotensin II (Ang II) and noradrenaline (NA) in rabbits feed on a high fat diet. Rabbits were feed with either normal rabbit chow (CD) or a high fat diet containing 6,67% corn oil and 3,33% lard (FD) ad libitum for 12 weeks. Thoracic aorta was excised, rings were cut and mounted in an organ bath to register isometric contractions in endothelium intact (E+) or endothelium removed (E-) arteries. One cumulative dose response curves (CDRC) to acetylcholine (Ach) was performed. After washing, one CDRC to NA or AngII was performed in E(+) and E(-) arteries. In other groups, E(+) arteries were incubated with indomethacin 10-5 M or miconazol 10-6 M or L-NAME 10-4 M before CDRC to NA or Ang II. Results: affinity to Ach was lower (pD2: 6.82±0.14 vs 7.08±0.09, p<0.05; n=12) and maximal contractile response (Emax) was unchanged in FD arteries. Emax to AngII (FD: 2877±452 vs CD: 5282±269 mg) and NA (FD: 7630±798 vs CD: 11675±804 mg) was blunted in (E+) but not in E(-) arteries (AngII-FD: 4250±550 vs CD: 4293±431 mg; NA-FD: 13361F±1257 vs CD:11970±571 mg). Shift to the right of CDRC to Ang II and NA was observed both in E(+) and E(-) in FD with respect to CD. L-NAME prevented the decrease in Emax (FD: 12041±250 mg) and affinity to NA. However, neither indomethacin nor miconazol nor L-NAME prevented the decrease on Ang II response. Conclusions: high fat diet blunted NA and AngII contractile response. This phenomenon was endothelium dependent. Mechanism of NA-decreased response depends on NO release but mechanism of Ang II remains to be elucidated.