The effect of exercise training on response of resistance arteries in hypertension induced by nitric oxide synthase inhibition

ABSTRACTThe increase in blood pressure during hypertension leads to importantdamage as coronary heart disease, heart failure and renal diseases. Endothelialdysfunction, considered to be an important hypothesis for induction of essentialhypertension, was clearly demonstrated in humans and experimental animals withhypertension. Regular physical training has blood pressure lowering effects inhypertensive subjects and rats with hypertension in some experimental hypertensionmodels. It was also revealed that aerobic exercise training also leads to a decreasein blood pressure in hypertension induced by inhibition of nitric oxide (NO)production, which is a potent vasodilator. The effect of exercise and probablealterations in response of resistance arteries of hypertensive rats was investigated inpresent study with a foresight that resistance arteries have important role inregulation of blood pressure.The rats were divided into four groups as follows: sedentary, exercise,training and non-training hypertensive. Hypertension was induced by oraladministration of a non-selective NO synthase enzyme inhibitor [Nω-nitro-L-argininemethyl ester (L-NAME), 25 mg.kg-1.day-1] in daily drinking water for a period of 6consecutive weeks. Training protocol was performed as swimming for 1 hour dailyand 5 days in a week, concomitantly with hypertension in exercising hypertensivegroup. Blood pressure was monitored periodically by a non-invasive tail-cuff method.The responses of resistance arteries, obtained from exercising striated muscle, wereevaluated using wire myography and organ bath equipment, allowing cannulation.The expression of three isoforms of NO synthase enzyme in skeletal muscle tissueand its arteries was determined by Western blot analysis.Blood pressure values in both hypertensive groups were higher than those ofsedentary group while exercise training induced a significant decrease in bloodpressure of exercising hypertensive animals. Resistance arteries with intactendothelium exhibited a decreased relaxation response to acetylcholine in presenceof either L-arginine or L-NAME in hypertensive group. Noradrenaline inducedcontraction responses and sodium nitroprussid related relaxation patterns weresimilar between the groups in both protocols with intact and denuded endothelium.Acetylcholine induced relaxation responses were also not different between thegroups in experiments with intact endothelium, where production of all vasodilatormediators was blocked and separately when soluble guanylate cyclase wasinhibited. Exercise training led to an improvement of flow mediated vasodilation inexercising hypertensive group and L-NAME incubation apparently ceased therelaxation responses induced by flow. eNOS expression was found to be higher inboth exercising groups in accordance with the findings for relaxation responses.nNOS contents of muscle tissues and vessels were not different between the groupsand iNOS expresson in muslce samples was also unaltered in experimental groups.In conclusion, the blood pressure lowering effect of regular physical trainingduring hypertension, induced by chronic NOS inhibition, was confirmed in thepresent study. However, by considering the significant increase in endothelial NOSexpression by exercise training, it is possible to indicate for an increased role of NOdependent relaxation pathway in exercising hypertensive rats.Key words: hypertension, L-NAME, exercise, NOS, myographv