Cardiovascular and autonomic modulation in trained rats: effects of iNOS inhibition and oxidative balance in the rostroventrolateral medulla

We proposed to investigate the participation of the inducible nitric oxide synthase (iNOS) on glutamatergic neurotransmission and the oxidative profile in the rostral ventrolateral medulla (RVLM) in trained rats. Wistar rats were submitted to physical training (T) protocol or sedentary (S) for 4 weeks. After the last swimming session, the animals were submitted to guide cannulae implantation directed to RVLM. After 3 days of surgical recovery, femoral artery and vein catheterization were performed for direct recording of mean arterial pressure (MAP) and heart rate (HR). The acquired cardiovascular data underwent spectral analysis (Cardio Series®). An inhibitor of iNOS (aminoguanidine, 250pmol/100nl) was unilaterally microinjected into the RVLM. Other animals received microinjection of glutamate (5nmol/100nl) in RVLM, before and after of the aminoguanidine. Bilateral punchs of RVLM were collected for analysis of iNOS gene expression (real‐time PCR); quantification of reduced glutathione and lipid peroxidation (spectrophotometer); iron‐reducing antioxidant (FRAP) and ABTS radical scavenger (Multiskan GO ThermoScientific®). T Animals presented a reduction in the gene expression of iNOS in RVLM associated to rest bradycardia (S: 371±8 vs . T: 312±8 b/min, r 2 = 0.58) and higher antioxidant capacity (FRAP; S: 5±1 vs . T: 9±1.3 nmol Trolox Eq/mg protein). Swimming improved baroreflex sensitivity (S: 1.04±0.06 vs . T: 2.4±0.28 ms 2 /mmHg 2 ) and lower sympathovagal ratio (LF/HF, S: 0.6±0.09 vs . T: 0.2±0.02). In T rats, the inhibition of iNOS in RVLM caused a lower pressor response (ΔMAP: S: 32±3 vs . T: 20±2 mm/Hg) and tachycardia (ΔHR: S: 55±4 vs . T: 43±1 b/min), abolishing previous differences in HR variability between groups. The microinjection of glutamate in RVLM of T group caused a lower pressor response (ΔMAP: S: 60±6 vs . T: 41±2 mmHg) and tachycardia (ΔHR: S: 90±4 vs . T: 58±3 b/min) and after iNOS inhibition in RVLM, we observed a greater glutamatergic response in T animals (ΔMAP: 69±3 mmHg). In conclusion, the cardiovascular benefits of physical training can be associated with decreased modulation by NO in RVLM via iNOS and also reduction of oxidative stress in this vasomotor center. Support or Funding Information CAPES (felowship) This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .