The effect of exercise training on carbon monoxide pathway of resistance arteries in hypertension model ınduced by nitric oxide synthase ınhibition

Endothelial dysfunction and nitric oxide (NO) deficiency play an important role in emergence and development of hypertension. It has been reported that spontaneously hypertensive rats feature less nitric oxide synthase (NOS) enzyme and reduced NO generation. Chronic inhibition of NOS enzyme in rats has become an animal model of hypertension beside others. Carbon monoxide (CO) is one of the relaxing mediators that have been highlighted in respect of its contribution to vascular tonus, functions and similarities to NO. CO may show a compensatory effect under the conditions in which NO production is reduced or not present. The blood pressure reducing effect of regular physical activity has been demonstrated in various experimental hypertension models. It has also been demonstrated in our laboratory that exercises during hypertension based on chronic NOS inhibition, reduce blood pressure significantly. In vascular arrangements that occur as a result of regular exercise, heme oxygenase/carbon monoxide (HO/CO) system is also affected. However, in hypertension model with NOS inhibition, the effect of the exercise to HO/CO system in vascular tissues is not known. Based on these data, the effect of regular swimming exercise on HO/CO system in the vascular tissues of normotensive and hypertensive rats was studied. For this purpose, animals were divided into 4 groups as control, exercise, hypertensive and hypertensive exercise. Hypertension was induced by oral administration of a non-selective NO synthase inhibitor [N?-nitro-L-arginine methyl ester (L-NAME), 25 mg.kg-1.day-1] dissolved in drinking water of animals, for a period of 6 consecutive weeks. Training protocol in exercise groups was performed as swimming for 1 hour daily and 5 days in a week, concomitantly with hypertension in exercising hypertensive group. Blood pressure of all groups was measured periodically by a non-invasive tail cuff method. Endogenous and exogenous responses of CO were examined in isolated preparations of gastrocnemius resistance and mesentery resistance arteries mounted to a wired myograph, and thoracic aort rings to organ bath equipment. In order to prove that rats were trained, citrate synthase enzyme activity was measured in red muscle fibers of vastus lateralis muscle. Furthermore, HO-1 and HO-2 expression in isolated arteries were determined by Western blot analysis. While blood pressure values were found to be high in both hypertensive groups compared to control group at the end of the examination, it was observed that blood pressure declined significantly in hypertensive exercise group compared to hypertensive group. Citrate synthase enzyme activity increased significantly in exercise and hypertensive exercise groups compared to their control groups. Endogenous CO relaxation responses of vessel rings were not different between the groups apart from the increase in thoracic aorta in control rats that performed exercise. Thoracic aorta HO-1 expression was significantly higher in both exercise groups. There was no difference between the groups in vasodilation in responses to exogenous CO in vessel rings. While CO demonstrated its effect in thoracic aorta by means of both sGC and K+ channels, it did so by means of K+ channels in gastrocnemius and mesentery resistance arteries. According to the results of our study, the lack of a positive effect of regular physical activity on relaxation responses in NOS inhibition hypertension model proves that HO/CO system does not function in compensatory manner in this hypertension model.Key words:hypertension, L-NAME, exercise, carbon monoxide, hemeoxygenase, nitricoxide, nitric oxide synthase, myograph