Moderate Physical Exercise Activates ATR2 Receptors, Improving Inflammation and Oxidative Stress in the Duodenum of 2K1C Hypertensive Rats

Abstract

Background: In addition to the cardiovascular and renal systems, the gastrointestinal tract also contains angiotensin ATR1a, ATR1b, and ATR2. We previously observed that the 2Kidney-1Clip hypertension model elicits physical exercise and gastrointestinal dysmotility, which is prevented by renin-angiotensin system blockers. Here, we investigate the effect of physical exercise on inflammation, stress biomarkers, and angiotensin II receptors in the duodenum of 2K1C rats.Methods: Arterial hypertension was induced by the 2K1C surgical model. The rats were allocated in Sham, 2K1C, or 2K1C+Exercise groups. One week after surgery, they were submitted to a physical exercise protocol (running 5x/week, 60min/day). Next, we assessed their intestinal contractility, cytokine levels (TNF-α, IL-1β, and IL-6), oxidative stress levels (MPO, GSH, MDA, and SOD), and the gene expression of angiotensin receptors (ATR1A, ATR1B, and ATR2).Results: In comparison with the Sham group, the 2K1C arterial hypertension decreased (p<0.05) the intestinal contractility. In comparison with 2K1C, the 2K1C+Exercise group exhibited lower (p<0.05) MPO activity (22.04±5.90 vs. 78.95±18.09 UMPO/mg tissue) and higher (p<0.05) GSH concentrations in intestinal tissues (67.63±7.85 vs. 31.85±5.90mg NPSH/mg tissue). The 2K1C+Exercise group showed lower (p<0.05) cytokine levels in the intestine than 2K1C rats. In comparison with the Sham group, the 2K1C+Exercise rats showed higher (p<0.05) gene expression of ATR2 in the duodenum.Conclusion: 2K-1C hypertension elicits an oxidative stress and inflammation process in the duodenum. Physical exercise modulates the expression twice as much of ATR2 receptors, suggesting possible anti-inflammatory and antioxidant effects induced by exercise.

Histomorphometry Changes and Decreased Reactivity to Angiotensin II in the Ileum and Colon of Streptozotocin-Induced Diabetic Rats

“…Ang II activates both receptors in the smooth muscle cells but also presynaptic receptors in other cells crucial for colonic function, an intricate network that has been reported to be altered in the diseased colon [ 27 , 29 , 54 ]. Regarding Ang II-mediated effects, it is known that contractile responses in intestinal smooth muscle occur mainly through the activation of AT 1 R, while AT 2 R’s role according to our group and others, seems to be more important under pathological conditions [ 27 , 55 , 56 ]. Not surprisingly, we observed that the AT 1 R antagonist (candesartan, 10 nM) completely abolished AngII-mediated contractile response in the ileum and all colon segments of both control and diabetic animals.…”

P2X7 receptor antagonist improves gastrointestinal disorders in spontaneously hypertensive rats

“…However, the role of hypertension on inflammation and oxidative stress affecting the GI tract still lacks consistent experimental evidence. Our research group was pioneering to show increases in pro-inflammatory cytokines and pro-oxidant markers in the duodenum of rats with 2K1C-induced hypertension ( 12 ). Here, we aimed at further characterizing the alterations of oxidative/nitrosative stress and inflammatory biomarkers in the gastric fundus, duodenum, and colon of SHR rats, which might have a functional impact on GI motility, namely on solid GE.…”

“…MPO activity in the resuspended pellet was evaluated by measuring the change in absorbance at 450 nm using o-dianisidine dihydrochloride and 1% hydrogen peroxide. The results are reported as units of MPO per mg of tissue (UMPO/mg of tissue) ( 12 ).…”

“…After 10-min, the absorbance of the samples was measured at 540 nm. The results are reported as micromoles of NOx ( 12 ).…”

“…The solution was then transferred to an ELISA plate, followed by the addition of the Griess reagent, performed in an ELISA reader at 550 nm. The value of the SOD unit (USOD/µg tissue) was calculated ( 12 ).…”