Exercise Training Alters the Balance Between Vasoactive Compounds in Skeletal Muscle of Individuals With Essential Hypertension

Abstract

Abstract-The effects of physical training on the formation of vasodilating and vasoconstricting compounds, as well as on related proteins important for vascular function, were examined in skeletal muscle of individuals with essential hypertension (nϭ10). Muscle microdialysis samples were obtained from subjects with hypertension before and after 16 weeks of physical training. Muscle dialysates were analyzed for thromboxane A 2 , prostacyclin, nucleotides, and nitrite/nitrate. Protein levels of thromboxane synthase, prostacyclin synthase, cyclooxygenase 1 and 2, endothelial nitric oxide synthase (eNOS), cystathionine-␥-lyase, cytochrome P450 4A and 2C9, and the purinergic receptors P2X1 and P2Y2 were determined in skeletal muscle. The protein levels were compared with those of normotensive control subjects (nϭ12). Resting muscle dialysate thromboxane A 2 and prostacyclin concentrations were lower (PϽ0.05) after training compared with before training. Before training, dialysate thromboxane A 2 decreased with acute exercise, whereas after training, no changes were found. Before training, dialysate prostacyclin levels did not increase with acute exercise, whereas after training there was an 82% (PϽ0.05) increase from rest to exercise. The exercise-induced increase in ATP and ADP was markedly reduced after training (PϽ0.05). The amount of eNOS protein in the hypertensive subjects was 40% lower (PϽ0.05) than in the normotensive control subjects, whereas cystathionine-␥-lyase levels were 25% higher (PϽ0.05), potentially compensating for the lower eNOS level. We conclude that exercise training alters the balance between vasodilating and vasoconstricting compounds as evidenced by a decrease in the level of thromboxane, reduction in the exercise-induced increase in ATP and a greater exercise-induced increase in prostacyclin. 4,5,6 Thus, the general beneficial effects of training on vascular function in this patient group are well documented. A main focus in the literature has been on the role of the endothelial nitric oxide synthase (eNOS) system for vascular function in essential hypertension, 1-3 and studies have shown an improved eNOS function with training that could contribute to a reduced vascular tone. 5,6 Nonetheless, the effect of hypertension and training on eNOS protein or NO formation in skeletal muscle of individuals with essential hypertension has not been clarified.The regulation of vascular tone in skeletal muscle is, however, not only dependent on NO but also on several other vasodilating and vasoconstricting compounds, of which many show interactions with NO. 7-10 Studies on the effect of training and hypertension on these vasoactive systems are, however, lacking in the literature, and such data provide an important addition to the existing literature.Several metabolites in the arachidonic acid pathway, eg, thromboxane A 2 (TXA 2 ), prostacyclin (PGI 2 ), 11,12-eicosatrienocic acid, and 20-hydroxyeicosatetraenoic acid, have been shown to be of importance for the regulation of vascular tone. 11-13 TXA 2 a...

Cardiovascular Adaptations to Exercise Training

“…A large number of human (66,117,161) (136,352). It should be noted that exercise training also has been shown to increase levels of neuronal NOS (nNOS) (135,314,315,408).…”

“…As described above, prostacyclin has been proposed to interact closely with NO in a manner where prostacyclin can compensate for a lack of NO and vice versa (40,291). Studies have shown that a period of exercise training increases the protein concentration of prostacyclin synthase and COX-1 in skeletal muscle tissue (135,175) although this has not been observed in all studies (161). In animal studies, training-induced improvements in endothelial dependent vasodilatation via bradykinine and acetylcholine are partly dependent on prostaglandins (86,87).…”

“…In animal studies, training-induced improvements in endothelial dependent vasodilatation via bradykinine and acetylcholine are partly dependent on prostaglandins (86,87). Moreover, in individuals with essential hypertension, training enhances the increase in muscle interstitial prostacyclin in response to adenosine infusion (175) and improves the balance between basal prostacyclin and thromboxane levels in the muscle interstitium (161). Therefore, although relatively limited data is available on the effect of training on the prostaglandin system, evidence point in the direction of that this system contributes importantly to the training-induced improvement in vascular adaptations.…”

“…Measurements of ATP in the muscle interstitium have revealed inconsistent findings. In aged men, ATP levels have been reported to be higher in life-long trained compared to sedentary men (295) whereas in hypertensive individuals reduced interstitial ATP levels were observed after training (161). Moreover, in young healthy men, a period of immobilization by casting of one leg was shown to reduce the exercise-induced increase in inerstitial ATP levels (292).…”

“…An impaired balance between vasodilating and vasoconstricting prostanoids is thought to be a contributing factor in the development of vascular dysfunction in cardiovascular disease (444). Limited evidence exist for the effect of exercise training on the balance of vasodilating and constricting prostanoids in humans but there are indications in the literature that exercise training may improve the prostanoid balance toward more vasodilators (161,413).…”