In summary, exercise training markedly elevates VEGF protein levels in muscle tissue, increases exercise-induced VEGF release from muscle and the cell proliferative effect of muscle dialysate. These alterations are paralleled by a lowering of blood pressure and an increased capillary-per-fiber ratio, but unaltered capillary density.

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...

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These results indicate that cyclin D-cdk4/6-dependent phosphorylation of pRb and activation of E2F is necessary for hypertrophic growth in cardiomyocytes, whereas cyclin E-cdk2 kinase is not necessary for hypertrophy but regulates endoreplication in these cells. The data support the notion that hypertrophic growth of cardiomyocytes involves a partial progression through the G1 phase of the cell cycle