Exercise improves vascular relaxation mediated by sGC/cGMP via inhibition of Rho‐Kinase signaling in eNOS −/− mice.

AIM: This study evaluated the vascular reactivity in exercised (TR) wild‐type (WT) and endothelium NO synthase knockout (eNOS −/−) mice. METHODS: Mice were exercised on a treadmill, at a speed of 10 m/min, 60 min/day, 5 days/week. After 8 weeks of training, aorta was removed and rings were mounted in myographs. Data were recorded in a PowerLab system. RESULTS: Acetylcholine (ACh) relaxed aorta with similar potency in sedentary (SD) and TR WT mice (pEC50: 6.98 ± 0.05 and 6.94 ± 0.09, respectively). In eNOS −/− mice, relaxation to ACh was completely abolished in both SD and TR mice. The pEC50 and maximum response (EMAX) to sodium nitroprusside (SNP) were increased in eNOS −/− SD mice (pEC50: 8.51 ± 0.02; EMAX: 101 ± 2%) compared to WT SD (pEC50: 7.97 ± 0.05; EMAX: 63 ± 8%). Moreover, there was an increase in the EMAX of SNP in WT TR mice (90 ± 4%) and in the pEC50 of eNOS (−/−) TR mice (8.89 ± 0.02). The potency of the Rho‐kinase inhibitor Y‐27632, was reduced in eNOS −/− SD compared to WT SD mice (pEC50: 6.06 ± 0.11 vs 6.53 ± 0.10, respectively). However, exercise prevented the impaired relaxation to Y‐27632 in eNOS −/− mice (pEC50: 6.49 ± 0.06). CONCLUSION: These results suggest that, in eNOS −/− mice, exercise improves relaxing responses of the aorta by increasing the soluble guanylyl cyclase/cyclic GMP pathway sensitivity and by decreasing Rho‐kinase pathway sensitivity. Financial Support: HL‐74167.