Increase In Forearm Vascular Resistance Research Articles

Forearm vascular resistance responses to the Valsalva maneuver in healthy young and older adults.

Effective end-organ peripheral vascular resistance responses are critical to blood pressure control while upright, and prevention of syncope (fainting). The Valsalva maneuver (VM) induces blood pressure decreases that evoke baroreflex-mediated vasoconstriction. We characterized beat-to-beat forearm vascular resistance (FVR) responses to the VM in healthy adults, evaluated the impact of age and sex on these responses, and investigated their association with orthostatic tolerance (OT; susceptibility to syncope). We hypothesized that individuals with smaller FVR responses would be more susceptible to syncope. Healthy young (N = 36; 19 women; age 25.4 ± 4.6years) and older (N = 21; 12 women; age 62.4 ± 9.6years) adults performed a supine 40mmHg, 20s VM. Graded 60° head-up-tilt with combined lower body negative pressure continued to presyncope was used to determine OT. Non-invasive beat-to-beat blood pressure and heart rate (finger plethysmography) were recorded continuously. FVR was calculated as mean arterial pressure (MAP) divided by brachial blood flow velocity (Doppler ultrasound) relative to baseline. The VM produces a distinctive FVR pattern that peaks (+137.1 ± 11.6%) in phase 2B (17.5 ± 0.3s) as the baroreflex responds to low-pressure perturbations. This response increased with age overall (p < 0.001) and within male (p = 0.030) and female subgroups (p < 0.001). Maximum FVR during the VM was significantly correlated with maximal tilt FVR (r = 0.364; p = 0.0153) and with OT when expressed relative to the MAP decrease in phase 2A (Max FVR (%)/MAP2A-1; r = 0.337; p = 0.0206). This is the first characterization of FVR responses to the VM. The VM elicits large baroreflex-mediated increases in FVR; small FVR responses to the VM may indicate susceptibility to syncope.

Skeletal muscle blood flow responses to hypoperfusion at rest and during rhythmic exercise in humans

We evaluated the contribution of changes in systemic arterial pressure and local vasodilation to blood flow restoration in contracting human muscles during acute hypoperfusion. Healthy subjects (n=10) performed rhythmic forearm exercise (10% and 20% of maximum) while a balloon in the brachial artery located above the elbow was inflated. Each trial included 3 min of rest, exercise, exercise with balloon inflation, and exercise after balloon deflation. Forearm blood flow (FBF) was measured using Doppler ultrasound. Blood pressure on both sides of the balloon was measured using a brachial artery catheter (distal pressure), and Finometer for proximal (systemic) arterial pressure. Balloon inflation during exercise reduced distal arterial pressure, and FBF fell 37-41%. There was also a surprising acute increase in forearm vascular resistance (distal pressure/FBF). This was followed by recovery of distal arterial pressure and forearm vasodilation that caused a marked (approximately 75%) restoration of flow that was not associated with significant changes in systemic arterial pressure. During validation trials (n=6) at rest and with exercise both balloon and brachial artery diameters were stable when the balloon was inflated. Our findings indicate that at these exercise intensities 1) the restoration of FBF during exercise with hypoperfusion relied primarily on local dilator responses in conjunction with restoration of distal perfusion pressure likely as a result of increased collateral flow around the elbow, and 2) a loss of pulsatile flow and elastic recoil in the forearm may have contributed to the acute increase in vascular resistance seen at the onset of hypoperfusion.

Attenuated peripheral vasoconstriction during an orthostatic challenge in older men

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. to examine tilt-induced peripheral vasoconstriction in the leg vascular bed of young and older men. 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. 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%). advancing age leads to an attenuated tilt-induced increase in calf vascular resistance, which may contribute to age-related orthostatic hypotension.

Alterations in forearm vascular reactivity in patients with septic shock

Patients with septic shock are haemodynamically unstable and suffer from vasodilation. Studying the human forearm vascular bed in patients with septic shock, we tested the hypothesis that the responses to regionally infused endothelium-(in)dependent vasodilators and vasoconstrictors are uniformly impaired. Forearm blood flow (FBF, venous occlusion plethysmography) and brachial arterial pressure were determined to calculate forearm vascular resistance (FVR) in eight consecutive sedated, mechanically ventilated patients with septic shock (APACHE II Score range 21-34, SOFA Score 11-16) and 11 healthy volunteers. Despite increased baseline FBF in patients with septic shock (6.1 (SD 1.5) ml x min(-1) x (100 ml of tissue)(-1) compared to 4.7 (1.4) in volunteers) the significant decreases in FVR seen in response to exogenous nitric oxide (nitroprusside) and acetylcholine did not differ between groups. However, compared to volunteers, mitigation of endogenous nitric oxide production by a low dose of N(G)-methyl-L-arginine acetate (L-NMMA) caused a significant increase (+6.7 mmHg x min x ml(-1)) in septic patients. Regional vasoconstriction in response to phenylephrine (FVR: +9.9 vs +30.7 mmHg x min x ml(-1) in controls) and angiotensin II (FVR: +9.0 vs +67.4 mmHg x min x ml(-1)) was markedly impaired. In contrast, vasopressin, in dosages evoking no vasoconstriction in volunteers, induced a significant increase in FVR in septic patients (+10.0 mmHg x min x ml(-1)). In the forearm of patients with septic shock, vasoconstriction by alpha1- and angiotensin II receptor agonists is selectively impaired, whereas the vasoconstrictor response to vasopressin is exaggerated. These findings exclude a generalised impairment of vasomotor activity in patients with septic shock and provide a rationale for vasopressin administration.

Reduced Defense of Central Blood Volume During Acute Lower Body Negative Pressure–Induced Hypovolemic Circulatory Stress in Aging Women

Elderly humans are more vulnerable to trauma and hemorrhage than young and elderly men and respond with decreased defense of central blood volume during acute experimental hypovolemia induced by lower body negative pressure (LBNP). However, these defense mechanisms have not been evaluated in elderly women. The aim of this study was to determine the effectiveness of compensatory responses to defend central blood volume during experimental hypovolemia in elderly and young women. Cardiovascular responses in 34 women, 12 elderly (66 ± 1 years) and 22 young women (23 ± 0.4 years), were studied during experimental hypovolemia induced by LBNP of 11 to 44 mmHg. Air plethysmography was used to assess the capacitance response (redistribution of peripheral venous blood to the central circulation) as well as net capillary fluid transfer from tissue to blood in the arm. Lower body negative pressure seemed to create comparable hypovolemia measured as total calf volume increase in elderly and young women. Heart rate increased less in elderly women (LBNP of 44 mmHg: 20 ± 2 vs. 37 ± 4%; P < 0.01) but with similar (%) increase in forearm vascular resistance. Mobilization of capacitance blood from the peripheral circulation was both slower and decreased by ∼60% in elderly women (P < 0.001), and net capillary fluid absorption from surrounding tissues was reduced by ∼40% (P < 0.01, LBNP of 44 mmHg). Elderly women responded with less increase in heart rate but with equal forearm vascular resistance (%) response during LBNP. Furthermore, the compensatory capacitance response was both slower and substantially decreased, and net capillary fluid absorption considerably reduced, collectively indicating less efficiency to defend central blood volume in elderly than in young women.

Acute water ingestion increases arterial blood pressure in hypertensive and normotensive subjects

In patients with severe autonomic dysfunction, water ingestion elicits an acute pressor response. Hypertension may be associated with changes in cardiovascular autonomic modulation, but there is no information on the acute effects of water ingestion in patients with hypertension. In this study, we compared the effect of acute water ingestion on haemodynamic and autonomic responses of hypertensive and normotensive individuals. Eight patients with mild hypertension were compared to 10 normotensive individuals. After 30 min resting in the supine position all subjects ingested 500 ml of water. At baseline and after water ingestion, venous blood samples for plasma volume determination were collected, and electrocardiographic tracings, finger blood pressure, forearm blood flow and muscle sympathetic nerve activity (MSNA) were obtained. Water ingestion resulted in similar and minor reduction in plasma volume. Systolic and diastolic blood pressure increased in both hypertensive (mean+/-s.d.: 19/14+/-6/3 mm Hg) and normotensive subjects (17/14+/-6/3 mm Hg). There was an increase in forearm vascular resistance and in MSNA. Heart rate was reduced (hypertensive: 5+/-1 beats/min, normotensive: 5+/-6 beats/min) and the high-frequency component of heart rate and systolic blood pressure variability was increased. In hypertensive and normotensive individuals, acute water ingestion elicits a pressor response, an effect that is most likely determined by an increased vasoconstrictor sympathetic activity, and is counterbalanced by an increase in blood pressure and heart rate vagal modulation.

Vasoconstrictive Response in the Vascular Beds of the Non-Exercising Forearm During Leg Exercise in Patients With Mild Chronic Heart Failure

Reduced exercise capacity may be related to decreased redistribution of blood flow from the non-exercising tissues to the exercising skeletal muscle in patients with mild chronic heart failure (CHF). In the present study 14 patients with mild CHF and 10 healthy subjects (N) underwent symptom-limited multistage-ergometer exercise, during which forearm vascular resistance (FVR), cardiac index (CI), systemic vascular resistance index (SVRI), and oxygen uptake (VO(2)) were measured non-invasively using the plethysmograph, impedance, and respiratory gas analysis methods, respectively. The VO(2) and CI at peak exercise were lower (p<0.01 each), and SVRI and FVR at both rest and peak exercise were higher in the CHF group than in N. However, both the percent increase in FVR and percent decrease in SVRI from the resting state to peak exercise were lower in CHF than N, and both of them correlated with not only peak VO(2), but also the corresponding resting value of FVR and SVRI (p<0.01 each). Redistribution of blood flow from the non-exercising tissues to the working skeletal muscles, which may participate in exercise capacity, can be blunted in CHF. The decreased vasoconstrictive response in the non-exercising tissues is intimately related to the increased resting vascular tone in CHF.

Tyramine-Induced Vasodilation Mediated by Dopamine Contamination

We reported previously that intravenous administration of tyramine induced a paradoxical forearm vasodilation and an increase in plasma dopamine, raising the possibility that dopamine is released by or converted from tyramine in vivo. Alternatively, tyramine can be nonenzymatically oxidized into dopamine in vitro, and this contamination may be responsible for the increase in plasma dopamine and forearm vasodilation. To distinguish between these possibilities, we measured the hemodynamic and neurohumoral effects of an intravenous infusion of a specially prepared dopamine-free tyramine solution in 8 normal volunteers at a dose that increased systolic blood pressure by approximately 25 mm Hg (from 107+/-5 to 133+/-5 mm Hg; P <0.001) and compared it with an equivalent dose of norepinephrine. Tyramine increased plasma norepinephrine (139+/-18 to 226+/-30 pg/mL; P <0.02), its intraneuronal metabolite dihydroxyphenylglycol (980+/-73 to 2245+/-206 pg/mL; P <0.001), and systemic vascular resistance, but not plasma dopamine or its intraneuronal metabolite dihydroxyphenylacetic acid. Tyramine and norepinephrine produced nonsignificant increases in forearm vascular resistance. We conclude that tyramine-induced forearm vasodilation reported in previous studies is explained by the presence of dopamine contamination in tyramine preparations. Intravenous administration of dopamine-free tyramine and norepinephrine produced equivalent systemic vasoconstriction. The forearm vasculature was not useful in monitoring the vasoconstrictive effects of either agent. The possibility of dopamine contamination needs to be considered when interpreting previously published studies using tyramine as a pharmacological tool to assess sympathetic function, and it must be avoided in future studies.

Mental stress opposes endothelium-dependent vasodilation in young healthy individuals

Mental stress has been shown to induce myocardial ischemia in people with coronary heart disease (CHD), both in the laboratory and in daily life. In order to investigate the role of the endothelium in the regulation of blood flow during stress, the endothelium-dependent (EDV) and endothelium-independent (EIDV) vasodilation was examined in the forearms of healthy people during a mental arithmetic test (MAT), a cold pressor test (CP) and an isometric handgrip test (ISO). A total of 10 young healthy volunteers (four men and six women, aged 20-25 years) underwent measurements of forearm vascular resistance (FVR) during local intraarterial infusions of methacholine (MCh; inducing EDV) and sodium nitroprusside (SNP; inducing EIDV) at rest and during the different forms of stress by the use of venous occlusion plethysmography. MAT induced a significant increase in FVR during MCh infusion (4 microg/min, from 3.5 +/- 0.7 at rest to 4.2 +/- 1.4 mmHg/ml per min per 100 ml tissue during MAT; p < 0.01), while FVR during SNP infusion was unchanged by MAT. CP induced a significant increase in FVR during infusions with both MCh and SNP compared to resting levels (p < 0.01 for both), while ISO induced a significant increase in FVR during MCh infusion (p < 0.05) and a smaller increase in FVR during SNP infusion. When the SNP to MCh FVR ratio was used as an index of endothelial function, only MAT impaired endothelial function significantly (p < 0.01). In conclusion, mental stress induced by an arithmetic task selectively opposed EDV in the forearms of young healthy people, while cold pressor and isometric handgrip tests induced a more general attenuation in vasodilatation.

The effect of systemic blood pressure on cardio-vascular reflexes in elderly subjects.

The evidence for impairment of cardiovascular reflexes by hypertension in elderly subjects is mixed. This study tested the hypothesis that baroreceptor- and non-baroreceptor-mediated responses in elderly subjects differed with hypertension. 54 elderly subjects were studied: 16 with combined hypertension (CT) (blood pressure 184 +/- 4/102 +/- 2 mmHg), 16 with isolated systolic hypertension (180 +/- 3/85 +/- 1 mmHg) and 22 normotensives (NT) (138 +/- 2/76 +/- 1 mmHg). All subjects performed isometric exercise with a handgrip dynamometer. Heart rate (HR), blood pressure and forearm vascular resistance (FVR) responses were then studied to 60 degrees head-up tilt and the cold face stimulus. Baseline FVR, and the response to isometric handgrip, were similar in all groups. Subjects with isolated systolic hypertension manifested greater increases in FVR with tilt (P<0.001), whilst the HR increment was greater in the NT group (P<0.001). Blood pressure changes with tilt were similar in the three groups. With the cold face stimulus (CFS) a rise in FVR of approximately 30% was seen in all groups and blood pressure rose modestly, with the largest increases being seen in the combined hypertensives. This study in elderly subjects indicates significant differences with hypertension in the response to tilt, with an impaired baroreceptor-cardiac reflex being compensated by an augmented baroreceptor-vascular response.

Decreased cardiopulmonary baroreflex sensitivity in Chagas' heart disease.

No study has been performed on reflexes originating from receptors in the heart that might be involved in the pathological lesions of Chagas' heart disease. Our study was undertaken to analyze the role of cardiopulmonary reflex on cardiovascular control in Chagas' disease. We studied 14 patients with Chagas' disease without heart failure and 12 healthy matched volunteers. Central venous pressure, arterial blood pressure, heart rate, forearm blood flow, and forearm vascular resistance were recorded during deactivation of cardiopulmonary receptors. By reducing central venous pressure by applying -10 and -15 mm Hg of negative pressure to the lower body, we observed (a) a similar decrease of central venous pressure in both groups; (b) a marked increase in forearm vascular resistance in the control group but a blunted increase in the Chagas' group; and (c) no significant changes in blood pressure and heart rate. To analyze cardiopulmonary and arterial receptors, we applied -40 mm Hg of lower-body negative pressure. As a consequence, (a) central venous pressure decreased similarly in both groups; (b) blood pressure was maintained in the control group, whereas in patients with Chagas' disease, a decrease in systolic and mean arterial pressure occurred; (c) heart rate increased in both groups; and (d) forearm vascular resistance increased significantly and similarly in both groups. Unloading of receptors with low levels of lower-body negative pressure did not increase forearm vascular resistance in patients with Chagas' disease, which suggests that the reflex mediated by cardiopulmonary receptors is impaired in patients with Chagas' disease without heart failure. Overall control of circulation appears to be compromised because patients did not maintain blood pressure under high levels of lower-body negative pressure.

Aging Is Associated with Endothelial Dysfunction in the Human Forearm Vasculature

Our objective was to examine the role of the endothelium in maintaining vascular tone in the basal as well as in the contracted state during aging. Responses to brachial artery infusion of acetylcholine in presence and absence of NG-nitro-L-arginine methyl ester (L-NAME) and to angiotensin II were studied in 11 young and 12 old white subjects. Strain gauge plethysmography was used to measure forearm vascular resistance (FVR). The dose of acetylcholine at 50% maximal observed decrease in forearm vascular resistance (EC50) was significantly higher (11.0 +/- 1.59 vs 7.07 +/- .65 microg/min, respectively; mean +/-SEM; P < .05) and the FVR at maximal acetylcholine effect (Emax) remained greater (12.6 +/- 1.75 vs 7.15 +/- 1.25 mm Hg/100 mL tissue volume/min; P < .02) in old compared with young subjects. Acetylcholine effect was significantly reversed by concomitant administration of L-NAME, as indicated by the increase in EC50 (old, 20.2 +/- 3.69; young, 11.9 +/- 1.68 microg/min). There was no age-related difference in sodium nitroprusside-induced decrease in FVR. The EC50 and Emax for angiotensin II-mediated increase in FVR were 7.87 +/- 1.15 and 8.36 +/- 1.00 ng/min (EC50) and 5.30 +/- .67 vs 6.56 +/-1.25 mm Hg/100 mL tissue volume/min (Emax), and these were not different in old and young subjects, respectively. These data indicate that aging is associated with impaired endothelial- dependent vascular relaxation and that this is selective, with no age-related change in endothelial-independent vascular relaxation or angiotensin II-mediated vascular contraction.

Orthostatic blood pressure changes and arterial baroreflex sensitivity in elderly subjects.

orthostatic hypotension in elderly people is often attributed to diminished afferent baroreflex sensitivity, but this has not been demonstrated. We examined the hypothesis that postural change in blood pressure is related to baroreflex sensitivity, independent of the confounding effect of baseline blood pressure. we studied 25 active, untreated elderly subjects free of postural symptoms (mean age 70 +/- 1 years): 16 with hypertension (clinic blood pressure 194 +/- 6/98 + 3 mmHg) and nine normotensive controls (clinic blood pressure 134 + 3/77 + 3 mmHg). We assessed baroreflex sensitivity from the heart rate and blood pressure responses to the Valsalva manoeuvre and a pressor and depressor stimulus (bolus phenylephrine injection or sodium nitroprusside infusion respectively). Subjects were then passively tilted to 60 degrees and maximum changes in systolic blood pressure, heart rate, forearm blood flow and forearm vascular resistance recorded. maximum change in systolic blood pressure with head-up tilt was correlated with supine systolic blood pressure (r = 0.60, P = 0.001). Maximum change in systolic blood pressure with orthostasis was greater in the hypertensive subjects (45 +/- 4 mmHg versus 29 +/- 6, P = 0.04) and the heart rate increment was less (16 +/- 2 bpm versus 24 +/- 4, P = 0.02). The increase in forearm vascular resistance with tilt was similar in the two groups (47 +/- 11 versus 38 +/- 7 units, P = 0.52). All three methods of assessing baroreflex sensitivity showed a reduction in the hypertensive subjects (all P < or = 0.02). Lower values of baroreflex sensitivity were related to greater falls in systolic blood pressure with tilt, after adjustment for the baseline level of systolic blood pressure. we found a relationship between baroreflex sensitivity and the systolic blood pressure fall with orthostasis, even after adjustment for prevailing systolic blood pressure. Despite equivalent changes in forearm vascular resistance with tilt, greater falls in systolic blood pressure were seen in hypertensive subjects than in normotensive controls, due in part to an inadequate baroreflex-mediated heart rate response. The postural fall in blood pressure often observed in elderly hypertensive subjects may be related to the reduced baroreflex sensitivity seen in this condition.

Forearm vasorelaxation in hypertensive renal transplant patients

To determine whether cyclosporine A-induced hypertension in renal transplant recipients is accompanied by impairment of endothelium-dependent vasodilatation, which has been suggested by in-vitro and in-vivo animal experiments. In-vivo endothelium-dependent and endothelium-independent vasodilatation, and plasma concentrations of vasoactive hormones in 16 renal transplant patients were determined while they were being treated with cyclosporine A, and 16 weeks later, after their treatment had been changed to azathioprine therapy. The vasodilator response of the forearm vascular bed was measured by strain gauge venous occlusion plethysmography during intra-arterial infusion of acetylcholine (endothelium-dependent vasodilatation) and nitroprusside (endothelium-independent vasodilatation). Postischemic reactive flow was measured after 10 min of arterial occlusion. In addition, plasma concentrations of norepinephrine, and the prostanoids prostaglandin E2 and thromboxane B2, and also concentration of cyclosporine A in blood, were measured. Glomerular filtration rate and renal blood flow were estimated 1 day before the plethysmography study during each treatment period. Upon changing from cyclosporine A to azathioprine treatment, mean arterial pressure fell significantly by 12+/-3% (P< 0.05). Glomerular filtration rate and renal blood flow increased by 13+/-5 and 19+/-8%, respectively (both P< 0.05), while renal vascular resistance fell by 48+/-11% (P< 0.01). Both baseline forearm blood flow and baseline forearm resistance did not change after conversion (5.7+/-0.7 versus 4.9+/-0.6 ml/100 ml/min, and 27.3+/-4.2 versus 26.2+/-3.2 arbitrary units). The absolute and relative forearm blood flow responses, and forearm vascular resistance responses to infusions of acetylcholine and nitroprusside were similar during treatments with cyclosporine A and azathioprine. Peak postischaemic forearm blood flow was 42+/-12% higher during cyclosporine A treatment than it was during azathioprine treatment (P< 0.05), but the minimal postischaemic forearm vascular resistance did not differ for these treatments. Plasma prostaglandin E2 and thromboxane B2 levels decreased by 34+/-7 and 45+/-8%, respectively, after changing treatment, but norepinephrine levels did not change. Our data indicate that cyclosporine A-induced hypertension in renal transplant recipients is not accompanied by an increase in forearm vascular resistance. In addition, changing from cyclosporine A to azathioprine treatment did not cause changes in endothelial vasodilator functioning, although mean arterial pressure decreased significantly. Our results do not support the hypothesis that attenuation of endothelial vasodilator functioning contributes to the development of cyclosporine A-induced hypertension.

Regulation of blood volume during training in post-menopausal women

In younger people the increase in aerobic capacity following training is related, in part, to blood volume (BV) expansion and the consequent improvements in maximal cardiac output. This training-induced hypervolemia is associated with a decrease in cardiopulmonary baroreflex (CPBR) control of peripheral vascular tone. To test the hypothesis that improvement in peak oxygen consumption (VO2peak) during training in older women is associated with specific central adaptations, such as BV expansion and a reduction in CPBR control of vascular tone. Seventeen healthy older women were randomized into training (N = 9, 71 +/- 2 yr) and control (N = 8, 73 +/- 3 yr) groups. The training group exercised three to four times per wk for 30 min at 60% peak heart rate for 12 wk and then 40-50 min at 75% peak heart rate for 12 wk. The control group participated in yoga exercises over the same time period. We measured resting BV (Evans blue dye), VO2peak, and the forearm vascular resistance response to unloading low pressure mechanoreceptors during low levels of lower body negative pressure (through -20 mm Hg) before and after aerobic training. The slope of the increase in forearm vascular resistance (response) per unit decrease in central venous pressure (stimulus) was used to assess CPBR responsiveness. Aerobic training increased VO2peak 14.2% from 24.2 mL x kg(-1) x min(-1) to 27.7 mL x kg(-1) x min(-1) (P < 0.05), a smaller improvement than typically seen in younger subjects. Blood volume (59.9 +/- 1.9 and 60.9 +/- 1.9 mL x kg[-1]) and CPBR function (-3.98 +/- 0.92 and -3.46 +/- 0.94 units x mm(-1) Hg) were similar before and after training. These data indicate that the inability to induce adaptations in CPBR function may limit BV expansion during training in older women. In addition, the absence of these specific adaptations may contribute to the relatively poor improvements in VO2peak in older women during short (10-12 wk) periods of training.

Cardiopulmonary and arterial baroreflex-mediated control of forearm vasomotor tone is impaired after acute stroke.

Elevated blood pressure (BP) levels are well recognized after acute stroke and are associated with increased BP variability. The underlying mechanisms producing such changes are unclear but may include abnormalities of baroreceptor-mediated control of heart rate and vasomotor tone. Lower body negative pressure (LBNP) can be used to assess the integrity of "low-pressure" cardiopulmonary and "high-pressure" arterial baroreceptor-derived responses by inducing nonhypotensive and hypotensive stimuli. Cardiovascular responses, including BP, heart rate, forearm blood flow, and forearm vascular resistance, to nonhypotensive and hypotensive LBNP were assessed in 13 consecutive stroke patients. Patients were studied within 72 hours of stroke (acute) and again at 10 to 14 days (subacute) and were compared with 13 control subjects individually matched for age, sex, and BP. At an LBNP of -10 mm Hg, BP was unchanged in all groups, but a significant increase in forearm vascular resistance occurred only in the control group (11 U [interquartile range, 7 to 15]; P < .05) compared with stroke patients in the acute (9 U [3 to 14]; P = NS) or subacute phases (7 U [2 to 12]; P = NS). After LBNP at -40 mm Hg, the reductions in systolic BP levels were similar in all groups (control: -9 mm Hg [-16 to -3]; acute stroke: -9 mm Hg [-22 to 3]; subacute stroke: -7 mm Hg [-35 to 20]), as was the associated increase in heart rate (control: 8 bpm ([4 to 11]; acute stroke: 6 bpm ([1 to 12]; subacute stroke: 9 bpm [2 to 19]). However, forearm vascular resistance increased significantly only in control subjects (20 U [9 to 30]; P < .01). The present study has identified abnormal vasomotor responses to LBNP after acute stroke, with an increase in FVR only being observed in control subjects in response to nonhypotensive and similar hypotensive levels of LBNP. In acute stroke patients, the stimulus of hypotensive LBNP appears to be compensated by an increase in cardiac output since there appears to be no increase in peripheral vascular resistance, unlike the changes seen in control subjects. However, the exact mechanisms for these changes are still unclear and are the subject of further study.

Venous and arterial reflex responses to positive-pressure breathing and lower body negative pressure.

We examined the relative importance of arteriolar and venous reflex responses during reductions in cardiac output provoked by conditions that increase [positive end-expiratory pressure (PEEP)] or decrease [lower body negative pressure (LBNP)] peripheral venous filling. Five healthy subjects were exposed to PEEP (10, 15, 20, and 25 cmH2O) and LBNP (-10, -15, -20, and -25 mmHg) to induce progressive but comparable reductions in right atrial transmural pressure (control to minimum): from 5.9 +/- 0.4 to 1.8 +/- 0.7 and from 6.5 +/- 0.6 to 2.0 +/- 0.2 mmHg with PEEP and LBNP, respectively. Cardiac output (impedance cardiography) fell less during PEEP than during LBNP (from 3.64 +/- 0.21 to 2.81 +/- 0.21 and from 3.39 +/- 0.21 to 2.14 +/- 0.24 l.min-1.m-2 with PEEP and LBNP, respectively), and mean arterial pressure increased. We observed sustained increases in forearm vascular resistance (i.e., forearm blood flow by venous occlusion plethysmography) and systemic vascular resistance that were greater during LBNP: from 19.7 +/- 2.91 to 27.97 +/- 5.46 and from 20.56 +/- 2.48 to 50.25 +/- 5.86 mmHg.ml-1.100 ml tissue-1.min (P < 0.05) during PEEP and LBNP, respectively. Venomotor responses (venous pressure in the hemodynamically isolated limb) were always transient, significant only with the greatest reduction in right atrial transmural pressure, and were similar for LBNP and PEEP. Thus arteriolar rather than venous responses are predominant in blood volume mobilization from skin and muscle, and venoconstriction is not intensified with venous engorgement during PEEP.

Reduced dietary potassium reversibly enhances vasopressor response to stress in African Americans.

Acute vasopressor responses to stress are adrenergically mediated and hence potentially subject to differential modulation by dietary potassium and sodium. The greater vasopressor responsiveness in blacks compared with whites might then be consequent not only to a high dietary salt intake but also to a marginally reduced dietary potassium intake. Under controlled metabolic conditions, we compared acute vasopressor responses to cold and mental stress in black and white normotensive men during three successive dietary periods: (1) while dietary potassium was reduced (30 mmol K+/70 kg per day) and salt was restricted (10 to 14 days); (2) while salt was loaded (15 to 250 mmol Na+/70 kg per day) (7 days); and (3) while salt loading was continued and potassium was either supplemented (70 mmol K+/70 kg per day) (7 to 21 days) in 9 blacks and 6 whites or continued reduced (30 mmol K+/70 kg per day) (28 days) in 4 blacks (time controls). At the lower potassium intake, cold-induced increase in forearm vascular resistance in blacks was twice that in whites during both salt restriction and salt loading. Normalization of dietary potassium attenuated cold-induced increases in both forearm vascular resistance and systolic and diastolic blood pressures in blacks but only in systolic pressure in whites. In blacks but not in whites, normalization of dietary potassium attenuated mental stress-induced increases in systolic and diastolic pressures. In normotensive blacks but not whites, a marginally reduced dietary intake of potassium reversibly enhances adrenergically mediated vasopressor responsiveness to stress. That responsiveness so enhanced over time might contribute to the pathogenesis of hypertension in blacks.

Endothelium-derived nitric oxide mediates hypoxic vasodilation of resistance vessels in humans.

Endothelium-derived nitric oxide (EDNO) contributes to basal systemic vascular resistance under normoxic conditions. The purpose of this investigation was to determine whether EDNO contributes to the regulation of limb vascular resistance during hypoxia in healthy humans. Forearm blood flow was assessed by venous occlusion plethysmography. Hypoxia was induced by delivering a mixture of N2 and O2 via a gas blender adjusted to reduce the PO2 to 50 mmHg. During hypoxia, forearm blood flow increased from 2.4 +/- 0.2 to 3.0 +/- 0.3 ml.100 ml-1.min-1 (P < 0.001), and forearm vascular resistance decreased from 38 +/- 3 to 29 +/- 3 units (P < 0.001). The nitric oxide synthase inhibitor NG-monomethyl-L-arginine (L-NMMA, 2,000 micrograms/min intra-arterially) was administered to eight subjects. The percent increase in forearm vascular resistance after administration of L-NMMA was greater during hypoxia than normoxia (67 +/- 14 vs. 39 +/- 15%, P < 0.05). L-NMMA reduced the forearm vasodilator response to hypoxia from 27 +/- 3 to 11 +/- 5% (P = 0.01). To exclude the possibility that this attenuated response to hypoxia was a consequence of vasoconstriction and not specific for nitric oxide synthase inhibition, six subjects received intra-arterial phenylephrine. Phenylephrine did not affect the vasodilator response to hypoxia (17 +/- 3 vs. 21 +/- 6%, P = NS). It is concluded that EDNO contributes to hypoxia-induced vasodilation in the forearm resistance vessels in healthy humans.

Vascular reactivity during combined ultrafiltration-haemodialysis: influence of dialysate sodium

It is well known that vascular reactivity is impaired during combined ultrafiltration-haemodialysis as compared to isolated ultrafiltration and haemofiltration, which might be related to differences in plasma osmolality. Therefore vascular reactivity was studied during combined ultrafiltration-haemodialysis in relation to sodium-related differences in plasma osmolality/tonicity. With each patient serving as his or her own control, nine stable dialysis patients (23–71 years) were studied during 2 h of combined ultrafiltration-haemodialysis (bicarbonate; UF rate 1.0 l/h)) at two different dialysate sodium concentrations: 134 and 144 mmol/l. Before dialysis as well as every 20 min during dialysis, blood pressure (Dinamap), heart rate (ECG), and forearm vascular resistance and venous tone (straingauge plethysmography) were measured. Relative blood volume was monitored continuously by an optical reflection method (Haemoguard 2000), while before and after dialysis blood was obtained for the estimation of plasma prostaglandin E2 High-sodium dialysis resulted in a significantly higher post-dialysis plasma sodium concentration (139.9 vs 135.0 mmol/l; P<0.01) while the decrease in relative blood volume was significantly smaller as compared to low-sodium dialysis (−8.4 vs −18.4%; P<0.01). There were no significant differences in the different haemodynamic parameters between the two treatment modalities. Both high- and low-sodium dialysis were associated with a significant increase in forearm vascular resistance while venous tone remained unchanged. Although there was no significant difference in plasma PGE2 between the two treatment modalities, PGE2 increased significantly only during low-sodium dialysis. We found no relationship between changes in PGE2 and vascular reactivity. We conclude that vascular reactivity during combined ultrafiltration-haemodialysis is not directly influenced by sodium-related changes in plasma tonicity. Although not directly studied, the reported improved haemodynamic stability with high-sodium dialysis is probably only mediated through a better preservation of plasma volume. Finally, an increase in plasma PGE2 as observed during low-sodium dialysis does not lead to a decrease in vascular tone.