Link between HO/NOS system and physical exercise

One enzyme system, which has been suggested to interact with HO is the NOS system. NO is synthesized from L-arginine in an enzymatic reaction catalyzed by NOS. Elevated NO levels have been shown to upregulate HO expression and inhibitors of the HO system inhibit NOS activity. HO activity may also regulate NO generation as NOS could provide heme a substrate for HO; and HO products can inhibit gene transcription, as demonstrated for bilirubin. Steensberg et al. found that NOS inhibition markedly reduced the exercise-induced expression of HO-1 mRNA in the human skeletal muscle, and infusion of the NO donor nitroglycerine augmented the expression of HO-1 mRNA attenuated by NOS blockade. It was suggested that NO is an upstream mediator that controls the exercise-induced expression of HO-1 mRNA expression in the human skeletal muscle.

The process underlying the mechanism of the cardioprotection induced by voluntary exercise needs to be elucidated. Recent studies have suggested that NO and HO upregulation might be of importance for the vascular complications in T2DM GK rat. The regular exercise activated the cNOS system and HO activity.

Furthermore, vigorous exercise increases the lymphocyte expression of the anti-inflammatory enzyme HO-1 at protein and mRNA levels. Lymphocytes play a pivotal role in inflammation-induced atherogenesis, and the increased transcription of the anti-inflammatory gene HO-1 in these cells following acute strenuous exercise would point toward a potentially important atheroprotective mechanism initiated by exercise. It was also found that there is no effect on the expression of the anti-inflammatory protein HO-1 in lymphocytes or in lymphocyte adhesion to cultured endothelial cells. Lymphocyte HO-1 expression is upregulated in response to prolonged demanding exercise, but eccentric contractions and a short exhaustive run have been shown to have no effect on HO-1 protein expression in leukocytes.