A decrease in heart rate was observed in animals treated with atenolol alone (286 ± 1 beats/min vs 301 ± 1 beats/min, before; n = 5) or associated to Ang-(1–7) (278 ± 1 beats/min vs 293 ± 1 beats/min, before; n = 5). As shown in Fig. 1B, on the eighth week of treatment there was no change in fasted glycemia in any of the
groups. Although atenolol alone had a trend to increase glucose levels, values were not statistically MK 2206 different. In order to evaluate lipid profile, at the end of the 14 weeks of treatment, total serum cholesterol, glycerol and triglycerides were measured. As shown in Fig. 1C, CD-Ang-(1–7) or atenolol alone did not alter serum triglycerides. However, animals
that received the association of CD-Ang-(1–7) and atenolol presented a ~60% lower values of total serum cholesterol (13 ± 3 mg/dL; Fig. 1D) than control animals that received CD alone, vehicle (38 ± 5 mg/dL; Fig. 1D). After oral administration of fat load, a hypertriglyceridemia was observed in control (vehicle; 92 ± 33 mg/dL vs 34 ± 3 mg/dL, before; NVP-BKM120 concentration Fig. 2A) or animals treated with atenolol, with a peak at 210 min (115 ± 17 mg/dL vs 52 ± 6 mg/dL, before; Fig. 2A). This alteration was not observed in the other groups: CD-Ang-(1–7) alone (52 ± 10 mg/dL vs 35 ± 6 mg/dL, before; Fig. 2A) or in CD-Ang-(1–7) associated with atenolol (48 ± 8 mg/dL 38 ± 4 mg/dL, before; Fig. 2A). Lipolysis was measured by the release of glycerol at baseline and after isoproterenol stimulation or insulin inhibition. As expected, isoproterenol
increased glycerol release in all groups (Fig. 2B). Although the basal lipolysis was similar in all treatments, after isoproterenol stimulation, the association of CD-Ang-(1–7) and atenolol induced a greater lipolysis (120 ± 14 mg/dL; Fig. 2B) as compared to atenolol alone (82 ± 7 mg/dL; Fig. 2B). Interestingly, the sensitivity of insulin was not changed by any treatment (Fig. 2C). Further, the sensitivity of insulin on glucose uptake was measured MycoClean Mycoplasma Removal Kit in adipocytes by radioactivity into the cells, since 2DOG can be transported but not oxidized. We have observed that all treatments did not change glucose uptake or the insulin sensitivity (Fig. 2C). Lipoprotein lipase (LPL) is an enzyme that hydrolyzes triglycerides components of lipoproteins providing free fatty acids (FFAs) and monoacylglycerol for being used by tissues. The release 3H-FFAs was quantified by liquid scintillation as an estimative of LPL activity. As shown in Fig. 2D, the LPL activity was not different in all groups studied. The present study showed, for the first time, the metabolic effect of an oral treatment with Ang-(1–7) associated with the β-blocker-atenolol.