Role of nitric oxide and prostanoids in the regulation of leg blood flow and blood pressure in humans with essential hypertension: effect of high-intensity aerobic training

Abstract

We examined the role of nitric oxide (NO) and prostanoids in the regulation of leg blood flow and systemic blood pressure before and after 8 weeks of aerobic high-intensity training in individuals with essential hypertension (n = 10) and matched healthy control subjects (n = 11). Hypertensive subjects were found to have a lower (P < 0.05) blood flow to the exercising leg than normotensive subjects (30 W: 2.92 ± 0.16 vs. 3.39 ± 0.37 l min(−1)). Despite the lower exercise hyperaemia, pharmacological inhibition of the NO and prostanoid systems reduced leg blood flow to a similar extent during exercise in the two groups and vascular relaxation to the NO-dependent vasodilator acetylcholine was also similar between groups. High-intensity aerobic training lowered (P < 0.05) resting systolic (∼9 mmHg) and diastolic (∼12 mmHg) blood pressure in subjects with essential hypertension, but this effect of training was abolished when the NO and prostanoid systems were inhibited. Skeletal muscle vascular endothelial NO synthase uncoupling, expression and phosphorylation status were similar in the two groups before and after training. These data demonstrate that a reduction in exercise hyperaemia in hypertensive subjects is not associated with a reduced capacity of the NO and prostanoid systems to induce vasodilatation or with altered acetylcholine-induced response. However, our data suggest that the observed reduction in blood pressure is related to a training-induced change in the tonic effect of NO and/or prostanoids on vascular tone.

Figure 1. Change in leg blood flow and vascular conductance with infusion of ACh

ACh was infused at 10 (ACh 1), 25 (ACh 2), and 100 μg min^-1 (kg leg mass)^-1 (ACh 3) in normotensive (n = 10) and hypertensive (n= 9) subjects before and after 8 weeks of aerobic exercise training. Values are means ±SEM. †Overall effect of training on leg vascular conductance in the hypertensive group.

Figure 2. Leg blood flow, mean arterial pressure, and leg vascular conductance during rest and one-leg knee-extensor exercise

Exercise was performed at 10, 20 and 30 W in normotensive (n = 9) and hypertensive (n = 9) subjects before and after 8 weeks of aerobic high-intensity training. Values are means ± SEM. *Overall difference between groups; †overall effect of training on mean arterial pressure in the hypertensive group and overall effect of training on leg blood flow in the normotensive group.

Figure 3. Leg blood flow, mean arterial pressure, and leg vascular conductance during rest and one-leg knee-extensor exercise with infusion of l-NMMA and indomethacin

Exercise was performed at 10, 20, and 30 W in normotensive (n = 9) and hypertensive (n = 8) subjects before and after 8 weeks of aerobic high-intensity training. Values are means ± SEM. *Overall difference between groups.

Figure 4. Reduction in LBF during one-leg knee-extensor exercise with infusion of l-NMMA and indomethacin (A) and mean arterial pressure during seated resting conditions (B)

HAemodynamic changes in normotensive (n = 9) and hypertensive (n = 8) subjects before and after 8 weeks of aerobic high-intensity training. Values are means ± SEM. *Significantly different from before training; †significantly different from control.

Figure 5. Arterial and venous NOx and leg NOx uptake during one-leg knee-extensor exercise at rest and 20 W

Plasma NOx in normotensive (n = 7) and hypertensive (n = 7) subjects before and after 8 weeks of aerobic high-intensity training. Values are means ± SEM. *Significantly different from normotensive; †significantly different from rest.

Figure 6. Protein expression of total eNOS, eNOS monomers, and the ratio between eNOS monomers and total eNOS (A), and protein expression of Thr⁴⁹⁵-phosphorylated eNOS, Ser¹¹⁷⁷-phosphorylated eNOS and nNOS (B)

Protein expression and phosphorylation status in normotensive (n = 11) and hypertensive (n = 10) subjects before and after 8 weeks of aerobic high-intensity training. Values are means ± SEM. †Significantly different from before training.