Short-term increases in intraluminal pressure reverse age-related decrements in endothelium-dependent dilation in soleus muscle feed arteries

Abstract

We tested the hypothesis that short-term increases in intraluminal pressure improve endothelium-dependent dilation and increase endothelial nitric oxide (NO) synthase (eNOS) expression in senescent soleus muscle feed arteries (SFA). SFA isolated from young (4 mo) and old (24 mo) Fischer 344 rats were cannulated and pressurized at 90 (p90) or 130 (p130) cmH(2)O for 4 h. At the end of the 4-h protocol, pressure in p130 SFA was lowered to 90 cmH(2)O for examination of endothelium-dependent (flow- or ACh-induced) vasodilation. Flow- and ACh-induced dilations were blunted in old p90 SFA relative to young p90 SFA. Pretreatment with increased pressure (p130) improved flow- and ACh-induced dilations in old SFA, such that vasodilator responses were similar to those in young SFA. In the presence of N(omega)-nitro-l-arginine (l-NNA) or l-NNA + indomethacin (Indo), flow-induced dilation was inhibited in old p130 SFA, such that the response was not greater than the response in old p90 SFA. In old p130 SFA, ACh-induced dilation was inhibited by l-NNA + Indo (not l-NNA alone). In a separate experiment, SFA were pressurized at 70, 90, 110, or 130 cmH(2)O for 4 h, and eNOS mRNA and protein content were assessed. Increased pressure induced eNOS mRNA expression in young (not old) SFA. eNOS protein content was not altered in young or old SFA. These results indicate that short-term increases in intraluminal pressure improve endothelium-dependent dilation in senescent SFA, in part by enhancing NO bioavailability; however, the beneficial effect was not associated with increased eNOS expression.

Fig. 1

Effect of aging on flow-induced dilation in soleus muscle feed arteries (SFA). All SFA were pressurized to 90 cmH₂O (p90) for 4 h before assessment of endothelial function. Values are means ± SE; n = 8–9 rats/group. ¹Significantly different from young p90, P ≤ 0.05.

Fig. 2

Effect of a short-term increase in intraluminal pressure on flow-induced dilation in young (A) and old (B) SFA. SFA were pressurized to 90 (p90) or 130 (p130) cmH₂O for 4 h. At the end of the 4-h treatment period, intraluminal pressure in p130 SFA was reset to 90 cmH₂O. Flow-induced dilation was then assessed in all SFA at an intraluminal pressure of 90 cmH₂O. Values are means ± SE; n = 8–9 rats/group. ¹Significantly different from p90, P ≤ 0.05.

Fig. 3

Flow-induced dilation in young (A) and old (B) SFA pressurized to 90 or 130 cmH₂O for 4 h. Vasodilator responses were assessed in the absence of enzyme inhibitors, in the presence of 300 µM N^ω-nitro-l-arginine (l-NNA), or in the presence of l-NNA + 5 µM indomethacin (Indo). Values are means ± SE; n = 8–9 rats/group. Significantly different from ¹p90 and ²p130, P ≤ 0.05.

Fig. 4

Effect of aging on ACh-induced dilation in SFA. All SFA were pressurized to 90 cmH₂O for 4 h before assessment of endothelial function. B, baseline diameter before the 1st dose of ACh. Values are means ± SE; n = 8–9 rats/group. ¹Significantly different from young p90, P ≤ 0.05.

Fig. 5

Effect of a short-term increase in intraluminal pressure on ACh-induced dilation in young (A) and old (B) SFA pressurized to 90 or 130 cmH₂O for 4 h. At the end of the 4-h treatment period, intraluminal pressure in p130 SFA was reset to 90 cmH₂O. ACh-induced dilation was assessed in all SFA at an intraluminal pressure of 90 cmH₂O. B, baseline diameter before the 1st dose of ACh. Values are means ± SE; n = 8–9 rats/group. ¹Significantly different from p90, P ≤ 0.05.

Fig. 6

ACh-induced dilation in young (A) and old (B) SFA pressurized to 90 or 130 cmH₂O for 4 h. Vasodilator responses were assessed in the absence of enzyme inhibitors, in the presence of 300 µM l-NNA, or in the presence of l-NNA + 5 µM Indo. B, baseline diameter before the 1st dose of ACh. Values are means ± SE; n = 8–9 rats/group. Significantly different from ¹p90 and ²p130, P ≤ 0.05.

Fig. 7

Sodium nitroprusside (SNP)-induced dilation in young (A) and old (B) SFA pressurized to 90 or 130 cmH₂O for 4 h. B, baseline diameter before the 1st dose of SNP. Values are means ± SE; n = 8–9 rats/group. Repeated-measures ANOVA revealed no significant between-group differences.

Fig. 8

Influence of intraluminal pressure on endothelial nitric oxide synthase (eNOS; A and B) and SOD-1 (C and D) mRNA expression in SFA isolated from young and old Fischer 344 rats. Values are means ± SE; n = 8 rats per group. SFA were pressurized at 70 (p70), 90 (p90), 110 (p110), or 130 (p130) cmH₂O for 4 h. *Significantly different from all other groups, P ≤ 0.05. ^#Significantly different from p70 and p110, P ≤ 0.05.

Fig. 9

Influence of intraluminal pressure on eNOS (A and B) and SOD-1 (C and D) protein content in SFA isolated from young and old Fischer 344 rats. Values are means ± SE; n = 9 rats per group. SFA were pressurized at 70, 90, 110, or 130 cmH₂O for 4 h. ANOVA revealed no significant differences.