Vascular nitric oxide: effects of exercise training in animals

Abstract

Exercise training is known to induce several adaptations in the cardiovascular system, one of which is increased skeletal muscle blood flow at maximal exercise. Improved muscle blood flow, in turn, could in part be accounted for by augmented endothelium-dependent, nitric oxide (NO)-mediated vasodilation. Studies have indeed demonstrated that endothelium-dependent, NO-mediated dilation of conductance-type vessels is augmented after endurance exercise training; recently, this adaptation has been extended into resistance-type vessels within rodent skeletal muscle. With the latter, however, it appears that only resistance vessels supplying muscle active during training sessions exhibit this adaptation. These findings in rats are in contrast to those from human studies, in which increased endothelium-dependent dilation has been observed in vasculatures not associated with elevated blood flow during exercise. Increased expression of endothelial NO synthase (eNOS) appears to underlie enhanced endothelium-dependent, NO-mediated dilation of both conductance and resistance vessels. Greater eNOS expression may also underlie the preventive and (or) rehabilitative effect(s) of exercise training on atherosclerosis, given that NO inhibits several steps of the atherosclerotic disease process. Thus, exercise training may induce adaptations that benefit both vasodilation and vascular health.

Fig. 1

Conductance (quotient of blood flow and perfusion pressure) in the red section of gastrocnemius muscle (RG; A), white section of gastrocnemius muscle (WG; B), mixed section of gastrocnemius muscle (MG; C), and soleus muscle (Sol; D). Values are means ± SE; sedentary group, open bars; exercise-trained group, filled bars. ACh, acetylcholine; SNP, sodium nitroprusside. *, Significantly different from control within the same group (p < 0.05); {, significantly different between tissues from sedentary and exercise-trained rats (p < 0.05). (From McAllister et al. 2005, reproduced with permission from J. Appl. Physiol., Vol. 98, p. 756, # 2005 The American Physiological Society.)

Fig. 2

Dose-dependent dilatory responses to increases in the flow of red gastrocnemius (RG) 2A arterioles (A), white gastrocnemius (WG) 2A arterioles (B), gastrocnemius (G) 1A arterioles (C), and soleus (Sol) 1A arterioles (D). Values are means ± SE; percent possible dilation was calculated as a fraction of the difference in diameter between arteriole with basal tone and without tone (in Ca²⁺-free perfusate). *, Significantly different between tissues from sedentary (Sed) and exercise-trained (Ex) rats (p < 0.05). (From McAllister et al. 2005, reproduced with permission from J. Appl. Physiol., Vol. 98, p. 758. # 2005 The American Physiological Society.)

Fig. 3

(A) eNOS protein expression in gastrocnemius (G) resistance vessels. GFA, G feed artery. Values are means ± SE; heights of bars represent the ratios of expression in tissues from exercise-trained (Ex) rats to that in tissues from sedentary (Sed) rats. Ex is significantly greater than Sed (p < 0.05) for RG 2A, 4A, and 5A arterioles; borderline significance (0.05 < p < 0.10) is also indicated. WG, white gastrocnemius; RG, red gastrocnemius. (B) SOD-1 protein expression in G resistance vessels. Note that Ex is significantly greater than Sed in only GFA. (From McAllister et al. 2005, reproduced with permission from J. Appl. Physiol., Vol. 98, p. 760. #2005 The American Physiological Society.)

Fig. 4

(A) eNOS protein expression in soleus (S) resistance vessels. SFA, soleus feed artery. Values are means ± SE; heights of bars represent the ratios of expression in tissues from exercise-trained (Ex) rats to that in tissues from sedentary (Sed) rats. Ex is not significantly greater than Sed (p < 0.05) in any arteriolar order. (B) SOD-1 protein expression in S resistance vessels. Note that Ex is not significantly greater than Sed in any arteriolar order. (From McAllister et al. 2005, reproduced with permission from J. Appl. Physiol., Vol. 98, p. 760, # 2005 The American Physiological Society.)

Fig. 5

Immunohistochemical staining of rabbit aorta for adhesion molecules (P-selectin and VCAM-1), inflammatory markers (MCP-1 and iNOS), and general morphology (hematoxylin–eosin stain). H, high cholesterol diet and sedentary; HE, high cholesterol diet and exercise-trained. Note the reduced expression of P-selectin and VCAM-1 in HE compared with H (P-selectin, D vs C; VCAM-1, H vs G), and less intimal thickness in HE compared with that in H (hematoxylin–eosin stain, T vs S). (From Yang et al. 2003, reproduced with permission from J. Appl. Physiol., Vol. 95, p. 1198. # The American Physiological Society.)