Attenuated peripheral vasoconstriction during an orthostatic challenge in older men.

BACKGROUND: orthostatic hypotension is common in older men and associated with morbidity and mortality. During orthostatic challenges, older men maintain their blood pressure by an augmented increase in total peripheral resistance. Changes in the leg vascular bed contribute importantly to blood pressure regulation during orthostatic challenges, partly because of blood pooling in the legs. Little is known about the contribution of the leg vascular bed to the augmented increase in total peripheral resistance. OBJECTIVE: to examine tilt-induced peripheral vasoconstriction in the leg vascular bed of young and older men. METHODS: we measured forearm and calf blood flow in 12 young and 12 older men, using venous occlusion plethysmography during 30 degrees head-up tilt (HUT). Forearm and calf vascular resistance were calculated as mean arterial blood pressure divided by blood flow. RESULTS: during HUT, calf and forearm vascular resistance increased in older and young men. The increase in forearm vascular resistance was similar between older (40 +/- 6%) and young men (51 +/- 12%). However, the increase in calf vascular resistance was lower in older (96 +/- 15%) than in young men (175 +/- 30%). CONCLUSION: advancing age leads to an attenuated tilt-induced increase in calf vascular resistance, which may contribute to age-related orthostatic hypotension.

Leg intravenous pressure during head-up tilt.

Leg vascular resistance is calculated as the arterial-venous pressure gradient divided by blood flow. During orthostatic challenges it is assumed that the hydrostatic pressure contributes equally to leg arterial, as well as to leg venous pressure. Because of venous valves, one may question whether, during orthostatic challenges, a continuous hydrostatic column is formed and if leg venous pressure is equal to the hydrostatic pressure. The purpose of this study was, therefore, to measure intravenous pressure in the great saphenous vein of 12 healthy individuals during 30 degrees and 70 degrees head-up tilt and compare this with the calculated hydrostatic pressure. The height difference between the heart and the right medial malleolus level represented the hydrostatic column. The results demonstrate that there were no differences between the measured intravenous pressure and the calculated hydrostatic pressure during 30 degrees (47.2 +/- 1.0 and 46.9 +/- 1.5 mmHg, respectively) and 70 degrees head-up tilt (83.9 +/- 0.9 and 85.1 +/- 1.2 mmHg, respectively). Steady-state levels of intravenous pressure were reached after 95 +/- 12 s during 30 degrees and 161 +/- 15 s during 70 degrees head-up tilt. In conclusion, the measured leg venous pressure is similar to the calculated hydrostatic pressure during orthostatic challenges. Therefore, the assumption that hydrostatic pressure contributes equally to leg arterial as well as to leg venous pressure during orthostatic challenges can be made.

Leg blood flow measurements using venous occlusion plethysmography during head-up tilt.

We tested whether venous occlusion plethysmography (VOP) is an appropriate method to measure calf blood flow (CBF) during head-up tilt (HUT). CBF measured with VOP was compared with superficial femoral artery blood flow as measured by Doppler ultrasound during incremental tilt angles. Measurements of both methods correlated well (r = 0.86). Reproducibility of VOP was fair in supine position and 30 degrees HUT (CV: 11%-15%). This indicates that VOP is an applicable tool to measure leg blood flow during HUT, especially up to 30 degrees HUT.

A causal role for endothelin-1 in the vascular adaptation to skeletal muscle deconditioning in spinal cord injury.

OBJECTIVE: Endothelin-1 (ET-1) contributes to the increased peripheral resistance in heart failure and hypertension. Physical inactivity is associated with cardiovascular disease and characterized by increased vascular tone. In this study, we assess the contribution of ET-1 to the increased vascular tone in the extremely deconditioned legs of spinal cord-injured (SCI) individuals before and after exercise training. METHODS AND RESULTS: In 8 controls and 8 SCI individuals, bilateral thigh blood flow was measured by plethysmography before and during the administration of an ET(A)/ET(B)-receptor blocker into the femoral artery. In SCI, this procedure was repeated after 6 weeks of electro-stimulated training. In a subset of SCI (n=4), selective ET(A)-receptor blockade was performed to determine the role of the ET(A)-receptors. In controls, dual ET-receptor blockade increased leg blood flow at the infused side (10%, P<0.05), indicating a small contribution of ET-1 to leg vascular tone. In SCI, baseline blood flow was lower compared with controls (P=0.05). In SCI, dual ET-receptor blockade increased blood flow (41%, P<0.001). This vasodilator response was significantly larger in SCI compared with controls (P<0.001). The response to selective ET(A)-receptor blockade was similar to the effect of dual blockade. Electro-stimulated training normalized baseline blood flow in SCI and reduced the response to dual ET-receptor blockade in the infused leg (29%, P=0.04). CONCLUSIONS: ET-1 mediates the increased vascular tone of extremely inactive legs of SCI individuals by increased activation of ET(A)-receptors. Physical training reverses the ET-1-pathway, which normalizes basal leg vascular tone.

Sympathetic nervous system contributes to the age-related impairment of flow-mediated dilation of the superficial femoral artery.

The physiological aging process is associated with endothelial dysfunction, as assessed by flow-mediated dilation (FMD). Aging is also characterized by increased sympathetic tone. Therefore, the aim of the present study is to assess whether acute changes in sympathetic activity alter FMD in the leg. For this purpose, the FMD of the superficial femoral artery was determined in 10 healthy young (22 +/- 1 yr) and 8 healthy older (69 +/- 1 yr) men in three different conditions: 1) at baseline, 2) during reduction of sympathetic activity, and 3) during sympathetic stimulation. Reduction of sympathetic activity was achieved by performing a maximal cycling exercise, leading to postexercise attenuation of the sympathetic responsiveness in the exercised limb. A cold pressor test was used to increase sympathetic activity. Nitroglycerin (NTG) was used to assess endothelium-independent vasodilation in all three conditions. Our results showed that, in older men, the FMD and NTG responses were significantly lower compared with young men (P = 0.001 and P = 0.02, respectively). In older men, sympathetic activity significantly affected the FMD response [repeated-measures (RM) ANOVA: P = 0.01], with a negative correlation between the level of sympathetic activity and FMD (R = -0.41, P = 0.049). This was not the case for NTG responses (ANOVA; P = 0.48). FMD and NTG responses in young men did not differ among the three conditions (RM-ANOVA: P = 0.32 and P = 0.31, respectively). In conclusion, in older men, FMD of the femoral artery is impaired. Local attenuation of the sympathetic responsiveness partly restores the FMD in these subjects. In contrast, in young subjects, acute modulation of the sympathetic nervous system activity does not alter flow-mediated vasodilation in the leg.

Preserved contribution of nitric oxide to baseline vascular tone in deconditioned human skeletal muscle.

Deconditioning is a risk factor for cardiovascular disease. Exercise reduces this risk, possibly by improving the vascular endothelial nitric oxide (NO) pathway. The effect of deconditioning on the NO pathway is largely unknown. This study was designed to assess baseline NO availability in the leg vascular bed after extreme, long-term deconditioning (spinal cord-injured individuals, SCI) as well as after moderate, short-term deconditioning (4 weeks of unilateral lower limb suspension, ULLS). For this purpose, seven SCI were compared with seven matched controls. Additionally, seven healthy subjects were studied pre- and post-ULLS. Leg blood flow was measured by venous occlusion plethysmography at baseline and during infusion of 5 incremental dosages of N(G)-monomethyl-L-arginine (L-NMMA) into the femoral artery. Sodium nitroprusside (SNP) was infused to test vascular responsiveness to NO. Baseline leg vascular resistance tended to be higher in SCI compared with controls (37+/-4 versus 31+/-2 arbitrary units (AU), P=0.06). Deconditioning altered neither the vasoconstrictor response to L-NMMA (increase in resistance in SCI versus controls: 102+/-33% versus 69+/-9%; pre- versus post-ULLS: 95+/-18% versus 119+/-15%), nor the vascular responsiveness to NO. In conclusion, two human in vivo models of deconditioning show a preserved baseline NO availability in the leg skeletal muscle vascular bed.

Preserved flow-mediated dilation in the inactive legs of spinal cord-injured individuals.

The aim of the study was to assess endothelial function, measured by flow-mediated dilation (FMD), in an inactive extremity (leg) and chronically active extremity (arm) within one subject. Eleven male spinal cord-injured (SCI) individuals and eleven male controls (C) were included. Echo Doppler measurements were performed to measure FMD responses after 10 and 5 min of arterial occlusion of the leg (superficial femoral artery, SFA) and the arm (brachial artery, BA), respectively. A nitroglycerine spray was administered to determine the endothelium independent vasodilatation in the SFA. In the SFA, relative changes in FMD were significantly enhanced in SCI compared with C (SCI: 14.1 +/- 1.3%; C: 9.2 +/- 2.3%), whereas no differences were found in the BA (SCI: 12.5 +/- 2.9%; C: 14.2 +/- 3.3%). Because the FMD response is directly proportional to the magnitude of the stimulus, the FMD response was also expressed relative to the shear rate. No differences between the groups were found for the FMD-to-shear rate ratio in the SFA (SCI:0.061 +/- 0.023%/s(-1); C: 0.049 +/- 0.024%/s(-1)), whereas the FMD-to-shear rate ratio was significantly decreased in the BA of SCI individuals (SCI: 0.037 +/- 0.01%/s(-1); C: 0.061 +/- 0.027%/s(-1)). The relative dilatory response to nitroglycerine did not differ between the groups. (SCI: 15.6 +/- 2.0%; C: 13.4 +/- 2.3%). In conclusion, our results indicate that SCI individuals have a preserved endothelial function in the inactive legs and possibly an attenuated endothelial function in the active arms compared with controls.

Preserved alpha-adrenergic tone in the leg vascular bed of spinal cord-injured individuals.

BACKGROUND: Supraspinal sympathetic control of leg vascular tone is lost in spinal cord-injured individuals, but this does not result in a reduced leg vascular tone: Leg vascular resistance is even increased. The aim of this study was to assess the alpha-adrenergic contribution to the increased vascular tone in the lower extremity in patients without central sympathetic control of leg circulation. METHODS AND RESULTS: Upper-leg vascular resistance responses to local infusion of incremental doses of phentolamine (a competitive antagonist of the alpha-adrenoceptor) into the femoral artery were determined in 10 spinal cord-injured individuals (SCI) and 8 healthy age-matched control subjects during local beta-adrenergic receptor blockade with propranolol. Basal leg vascular resistance was higher in SCI than in control subjects (41+/-6 arbitrary units [AU] versus 24+/-4 AU; P=0.034). The same accounts for minimal leg vascular resistance, assessed during reactive hyperemia, which was higher in SCI compared with control subjects (6.9+/-1.0 AU versus 2.5+/-0.2 AU; P<0.01). The maximal phentolamine-induced reduction in leg vascular resistance normalized to each individual's minimal resistance did not differ between the groups (68+/-17% and 51+/-4% for SCI and control subjects, respectively; P>0.1). A decline in mean arterial pressure was observed in both groups with increasing dosage of phentolamine. In response, baroreceptor-mediated vasoconstriction was observed in the noninfused leg of the control subjects, whereas in SCI individuals this reaction was absent. CONCLUSIONS: These results indicate that the alpha-adrenoceptor-mediated vascular tone in the leg is preserved in spinal cord-injured individuals without sympathetic supraspinal control.

Venous cuff pressures from 30 mmHg to diastolic pressure are recommended to measure arterial inflow by plethysmography.

Venous occlusion strain gauge plethysmography (VOP) is based on the assumption that the veins are occluded and arterial inflow is undisturbed by the venous cuff pressure. Literature is not clear concerning the pressure that should be used. The purpose of this study was to determine the optimal venous occlusion pressure at which the highest arterial inflow is achieved in the forearm, calf, and leg by using VOP. We hypothesized that, for each limb segment, an optimal (range of) venous cuff pressure can be determined. Arterial inflow in each limb segment was measured in nine healthy individuals by VOP by using pressures ranging from 10 mmHg up to diastolic blood pressure. Arterial inflows were similar at cuff pressures between 30 and 60 mmHg for the forearm, leg, and calf. Arterial inflow in the forearm was significantly lower at 10 mmHg compared with the other cuff pressures. In addition, arterial inflows at 20 mmHg tended to be lower in each limb segment than flow at higher cuff pressures. In conclusion, no single optimum venous cuff pressure, at which a highest arterial inflow is achieved, exists, but rather a range of optimum cuff pressures leading to a similar arterial inflow. Venous cuff pressures ranging from 30 mmHg up to diastolic blood pressure are recommended to measure arterial inflow by VOP.