Forearm Vascular Responses Research Articles

Acute vascular effects of estrogen in postmenopausal women.

Although hormone replacement therapy has been associated with reduction of cardiovascular events in postmenopausal women, the mechanisms that mediate this apparent benefit are unclear. Because improvement in vasomotor function may represent one of the beneficial effects of estrogen administration, we investigated the acute effects of physiological levels of estrogen on the vascular responses of estrogen-deficient postmenopausal women. The study included 40 postmenopausal women 60 +/- 8 years old (mean +/- SD), 20 of whom had one or more conditions associated with vascular dysfunction (hypertension, hypercholesterolemia, diabetes, or coronary artery disease). The forearm vascular responses to the endothelium-dependent vasodilator acetylcholine were studied before and during infusion of 17 beta-estradiol into the ipsilateral brachial artery. In 31 subjects, the effect of estradiol on the responses to the endothelium-independent vasodilator sodium nitroprusside was also studied. Women with risk factors for vascular dysfunction had significantly reduced vasodilator responses to acetylcholine (P = .01) and to sodium nitroprusside (P < .001) compared with healthy subjects. Intra-arterial infusion of 17 beta-estradiol increased the forearm venous estradiol concentration from 16 +/- 10 to 318 +/- 188 pg/mL, levels typical of reproductive-age women at midcycle, but caused no vasodilation. However, estradiol potentiated the forearm vasodilation induced by acetylcholine by 18 +/- 30% (P < .001) in women with risk factors for vascular dysfunction and by 14 +/- 23% (P = .03) in healthy women. Estradiol also potentiated the forearm vasodilation induced by sodium nitroprusside in women with risk factors for vascular dysfunction by 14 +/- 21% (P < .001) but not in healthy women. Physiological levels of 17 beta-estradiol selectively potentiate endothelium-dependent vasodilation in healthy postmenopausal women and potentiate both endothelium-dependent and endothelium-independent vasodilation in post-menopausal women with risk factors for atherosclerosis and evidence of impaired vascular function. These vascular effects may be partly responsible for the long-term benefit of estrogen therapy on cardiovascular events in postmenopausal women.

Forearm vascular responsiveness to alpha 1- and alpha 2-adrenoceptor stimulation in patients with congestive heart failure.

The alpha-adrenergic component of the sympathetic nervous system plays a major role in the pathophysiology, clinical manifestations, and natural history of human congestive heart failure (CHF). However, the functional integrity of vascular alpha 1- and alpha 2-adrenoceptors in CHF remains to be elucidated. The present study was designed to assess the vascular responsiveness of alpha 1- and alpha 2-adrenoceptors in patients with CHF. To evaluate alpha 1- and alpha 2-adrenoceptor responsiveness, we studied the effects of the regional infusion into the brachial artery of increasing doses of phenylephrine (a selective alpha 1-adrenoceptor agonist) and BHT 933 (a selective alpha 2-adrenoceptor agonist) on vascular responses in 12 healthy subjects and in 24 patients with CHF secondary to primary dilated cardiomyopathy or ischemic heart disease. Left ventricular ejection fraction was measured by radionuclide angiography, and forearm blood flow was determined by venous occlusion plethysmography. Phenylephrine reduced forearm blood flow in normal subjects from 5.2 +/- 0.9 to 2.5 +/- 0.6 mL per 100 mL of tissue/min (P < .05) at the highest dose (-50.8 +/- 4.8% versus baseline). A similar vasoconstriction was obtained in patients with CHF (from 3.5 +/- 0.5 to 1.5 +/- 0.2 mL per 100 mL of tissue/min (P < .05) (-58.7 +/- 5.0% versus baseline). The dose-response curves produced by phenylephrine in the two groups were comparable. The highest dose of BHT 933 reduced forearm blood flow in normal subjects from 5.3 +/- 0.9 to 2.3 +/- 0.6 mL per 100 mL of tissue/min (P < .05) (-59.0 +/- 4.9% versus baseline). In patients with CHF, a similar vasoconstriction was obtained (from 4.2 +/- 0.8 to 1.5 +/- 0.3 mL per 100 mL of tissue/min, P < .05, -62.1 +/- 6.5% versus baseline). The dose-response curves produced by BHT 933 also were comparable in the two groups. In patients with CHF, plasma concentrations of norepinephrine were significantly higher than in normal subjects. The results of the present study demonstrate that alpha 1- and alpha 2-adrenoceptor stimulations produced an equivalent vasoconstriction in patients with CHF and in normal subjects. This indicates that the vascular responsiveness to alpha-adrenoceptor agonists may be preserved in the limb vessels of patients with CHF.

Diminished vascular response to inhibition of endothelium-derived nitric oxide and enhanced vasoconstriction to exogenously administered endothelin-1 in clinically healthy smokers.

Smoking is a major risk factor for the development of atherosclerosis. Because endothelial dysfunction may be a marker for future atherosclerosis, we investigated the effects of smoking on endothelium-dependent control of vascular tone. The effects of brachial arterial infusions of NG-monomethyl-L-arginine (L-NMMA), a nitric oxide synthesis inhibitor; sodium nitroprusside; endothelin-1; and norepinephrine on forearm blood flow (strain-gauge plethysmography) were compared in 29 long-term smokers and 16 nonsmokers. The acute effects of smoking on systemic hemodynamics, plasma catecholamines, and forearm vascular responses to these compounds were investigated in smokers only. Smokers did not differ from nonsmokers (n = 16) regarding the vascular effects of sodium nitroprusside (n = 13) or vasoconstriction due to norepinephrine and endothelin-1 (n = 16). Low-dose endothelin-1-induced vasodilation, believed to reflect endothelial prostacyclin or nitric oxide release, was absent in smokers (n = 16), and their increase of forearm vascular resistance (FVR) after L-NMMA (n = 13) was impaired (35.6 +/- 27.9% versus 118.8 +/- 43.2%, P < .001). Short-term smoking (n = 11) increased blood pressure, heart rate, and plasma epinephrine concentrations (P < .05 or less); enhanced endothelin-1-induced vasoconstriction (delta FVR, 457 +/- 192% versus 254 +/- 143%, P < .01); and decreased norepinephrine-induced vasoconstriction (P < .05), but had no effect on the other interventions. Long-term smoking is associated with a diminished nitric oxide-dependent component of basal vascular tone and an impaired endothelium-dependent vasodilator response to low-dose endothelin-1 and short-term smoking enhances endothelin-1-induced vasoconstriction. Impaired endothelial control of vascular tone might reflect impairment of normal antiatherosclerotic endothelial functions in smokers, but the relevance of smoking-induced enhancement of endothelin-1 vasoconstriction remains to be determined.

Investigation of decreased availability of nitric oxide precursor as the mechanism responsible for impaired endothelium-dependent vasodilation in hypercholesterolemic patients

Objective. The purpose of this study was to determine whether the impaired endothelium-dependent vasodllation of hyperchoiesterolemic patients is due to decreased availability of l-arginine, the substrate for nitric oxide.Background. Patients with hypercholesterolemia have impaired endothelium-dependent vasodilation that is related to a defect in the endothelium-derived nitric oxide system. However, the precise location of this abnormality has not been determined.Methods. The study included 12 hypercholesterolemic patients (6men, 6 women; 52 ± 9 years old; serum cholesterol>240mg/dl) and 15 normal volunteers (8 men, 7 women; 50 ± 6 years old; serum cholesterol < 210 mg/dl. The forearm vascular responses to intraaterial infusion of acetylccholine, an endothelium-dependent vasodilator (7.5, 15, 30 μg/min), and sodium nitropruside, a direct smoth muscle dilator (0.8,1.6,3.2 μg/min) were studied before and during Infusion of l- or d-arginine (a stereoisomer of arginine that is not a nitric oxide precursor).Results. The response to acetylcholine was lower in hypercholesterolemic patients than in control sutjects. However, no significant difference was observed with sodium nitroprusside infusion. l-Arginine augmented the response to acetylcholine in normal subjects (maximal blood flow increased from 14.4 ± 7 to 18.9 ± 10 ml/min per 100 ml, p < 0.002). In contrast, in the hypercholesterolemic patients, only a mild but not significant improvement in the response to acetylcholine was observed with the infusion of l-arginine (maximal blood flow increased from 6.8 ± 4 to 8.4 ±5ml/min per 100ml; p = 0.161; however, a similar mild but not significant change was also observed with l-arginine (maximal blood flow increased from 6.8± 4 to 8.3 ± 4 ml/min per 100 ml, p = 0.07). l-Arginine did not modify the response to sodium nitroprusside in either group.Conclusions. The augmentation of endothelium-dependent vasodilation by l-arginine, the nitric oxide precursor, is defective in hypercholesterolemic patients. This supports the concept of an abnormal endothelium-derived nitric oxide system in hypercholesterolemia and indicates that decreased availability of nitric oxide substrate is not responsible for the impaired endothelial function in this condition.

Skeletal muscle vascular responses in human limbs to isometric handgrip

Studies of whole limb blood flow have shown that static handgrip elicits a vasodilatation in the resting forearm and vasoconstriction in the resting leg. We asked if these responses occur in the skeletal muscle vascular bed, and if so, what is the relative contribution of local metabolic versus other mechanisms to these vascular responses. Blood flow recordings were made simultaneously in the skeletal muscle of the resting arm and leg using the Xenon-washout method in ten subjects during 3 min of isometric handgrip at 30% of maximal voluntary contraction. In the arm, skeletal muscle vascular resistance (SMVR) decreased transiently at the onset of exercise followed by a return to baseline levels at the end of exercise. In the leg SMVR remained unchanged during the 1st min of handgrip, but had increased to exceed baseline levels by the end of exercise. During exercise electromyography (EMG) recordings from nonexercising limbs demonstrated a progressive 20-fold increase in activity in the arm, but remained at baseline in the leg. During EMG-signal modelled exercise performed to mimic the inadvertent muscle activity, decreases in forearm SMVR amounted to 57% of the decrease seen with controlateral handgrip. The present study would seem to indicate that vascular tone in nonexercising skeletal muscle in the arm and leg are controlled differently during the early stages of static handgrip. Metabolic vasodilation due to involuntary contraction could significantly modulate forearm skeletal muscle vascular responses, but other factors, most likely neural vasodilator mechanisms, must make major contributions. During the later stages of contralateral sustained handgrip, vascular adjustments in resting forearm skeletal muscle would seem to be the final result of reflex sympathetic vasoconstrictor drive, local metabolic vasodilator forces and possibly neurogenic vasodilator mechanisms.

Effects of fludrocortisone on sympathetic nerve activity in humans.

Fludrocortisone reduces plasma norepinephrine in healthy humans, but forearm vascular and pressor responses to norepinephrine are potentiated. The effects of fludrocortisone on sympathetic nerve activity in healthy humans are not known. To investigate these effects we evaluated muscle sympathetic nerve activity, heart rate, and arterial pressure in 11 healthy volunteers during three protocols: (1) before and on day 7 of fludrocortisone (0.4 mg/d) treatment with ad libitum diet (n = 6); (2) before and on day 7 of fludrocortisone (0.4 mg/d) or placebo with a 150 mmol/24 h (mEq/24 h) sodium diet (n = 7); and (3) before and on day 2 of fludrocortisone (0.4 mg/d) or placebo with a 150 mmol/24 h (mEq/24 h) sodium diet (n = 4). Placebo did not alter any parameter.(ABSTRACT TRUNCATED AT 250 WORDS)

Occurrence of presyncope in subjects without ventricular innervation.

1. To determine whether activation of the left ventricular C-fibre mechanoreceptors initiates the vasodepressor reflex that often causes syncope, we exposed six orthotopic cardiac transplant patients and six matched, healthy control subjects to progressively increasing lower body negative pressure until the onset of vasodepressor responses. 2. There was no significant difference (P = 0.78) between the central hypovolaemia tolerances of the cardiac transplant and the control groups. 3. The decrease in systolic blood pressure before the onset of vasodepressor reflexes was greater in the cardiac transplant group. The cardiac transplant group did not maintain diastolic blood pressure during central hypovolaemia. From baseline to the onset of vasodepression, there were no differences in leg circumference, forearm blood flow and forearm vascular resistance responses between the two groups. 4. We conclude that the left ventricular mechanoreceptors may not be the primary afferent trigger for syncope.

Inhibition of Nitric Oxide Synthesis in Forearm Vasculature of Insulin-Dependent Diabetic Patients: Blunted Vasoconstriction in Patients with Microalbuminuria

1. Microalbuminuria is a risk factor for cardiovascular disease in patients with insulin-dependent diabetes mellitus, and may be a marker of microvascular dysfunction including endothelial damage. The purpose of this study was to determine whether vasoconstrictor responses to NG-monomethyl-L-arginine, an inhibitor of endothelium-derived relaxing factor/nitric oxide biosynthesis, differ between healthy subjects and insulin-dependent patients with or without microalbuminuria. 2. Twenty-eight insulin-dependent diabetic patients (14 with normal albumin excretion, 14 with microalbuminuria) were studied under euglycaemic conditions, together with 14 healthy control subjects. Forearm vascular responses to brachial artery infusions of NG-monomethyl-L-arginine, sodium nitroprusside (an endothelium-independent nitrovasodilator) and carbachol (an endothelium-dependent vasodilator) were determined by strain gauge plethysmography. 3. Basal blood flow and vasodilator responses were similar in each group. NG-Monomethyl-L-arginine reduced blood flow by 41.3 +/- 2.3% (mean +/- SEM) in healthy control subjects, 34.0 +/- 3.4% in diabetic patients without microalbuminuria and 29.2 +/- 2.0% in diabetic patients with microalbuminuria. Diabetic patients differed from healthy subjects (P = 0.005), due to a difference between control subjects and microalbuminuric diabetic patients (P < 0.001). NG-Monomethyl-L-arginine did not influence nitroprusside responses but reduced carbachol responses in control subjects and normoalbuminuric diabetic patients but not in microalbuminuric diabetic patients. 4. These results provide evidence of abnormal endothelium-derived relaxing factor/nitric oxide biosynthesis in insulin-dependent diabetic patients with microalbuminuria.

Forearm arterial vascular responsiveness in insulin-dependent diabetic subjects

The vascular reactivity of forearm arterioles was measured in 16 control subjects (C) and 30 insulin-dependent diabetic (IDDM) subjects, 16 of whom were shown to have microvascular and/or neuropathic complications (DC) including 8 with autonomic neuropathy (DCa) and 14 were shown to be free of complications (DNC). Forearm blood flow was measured by strain gauge plethysmography basally, following a cold pressor stress and following a period of arterial occlusion (reactive hyperaemia). The tests were repeated 24 h later following aspirin treatment. Both C and DNC showed a significant reduction in blood flow in the cold pressor test (C 0.64 ± 0.12, DNC 0.89 ± 0.22 ml/100 ml forearm tissue/min reduction in flow P < 0.005), while DC showed no significant response. Reactive hyperaemia was significantly greater in C than in DNC or DC (8.37 ± 1.14, 5.51 ± 1.27 and 4.95 ± 0.75 ml/100 ml tissue/min, respectively, P < 0.02). In the DC group, DCa had significantly less response than those without autonomic neuropathy. Aspirin treatment restored the response of DNC but not DC to normal, suggesting that the abnormality in the former group may have been due to overproduction of a vasoconstrictive cyclooxygenase product (such as thromboxane A 2). It is concluded that the abnormalities of vasomotor responses in diabetic subjects are complex and are apparently dependent on autonomic neuropathy, humoral and perhaps structural changes.

Forearm vascular responses to baroreceptor unloading at the onset of dynamic exercise.

To determine the extent to which reflexes accompanying muscular exercise (associated with central command) interact with cardiopulmonary (CP) baroreceptor-mediated reflexes controlling forearm vascular resistance (FVR), we examined the forearm vasoconstrictor response at the onset of dynamic exercise, with and without CP baroreflex unloading, in 10 physically active men. CP baroreceptors were unloaded by application of lower body negative pressure (LBNP) at rest and during five 4-min bouts of supine exercise at 25 and 32 degrees C. Exercise intensities were 10 (essentially no load) and 100 W, and LBNP was applied at -10, -20, -30, and -40 mmHg during rest and at -20 and -40 mmHg during exercise. Resting FVR was 33.0 +/- 3.2 and 14.0 +/- 2.7 resistance units, and cardiac stroke volume (SV) was 117 +/- 7 and 126 +/- 9 ml/beat at 25 and 32 degrees C, respectively. We found a linear relationship between the increase in FVR and decrease in SV during LBNP; the slope of the relationship was significantly lower at 32 degrees C (FVR = 51.7-0.29SV) than at 25 degrees C (FVR = 123-0.79SV). At the onset of 100-W exercise without LBNP, FVR increased significantly to 50.2 +/- 9.0 and 21.2 +/- 3.2 units at 25 and 32 degrees C, respectively, whereas SV was unchanged. Application of -40-mmHg LBNP reduced SV significantly to 68 +/- 5 and 71 +/- 6 ml/beat and increased FVR significantly to 89.0 +/- 11.3 and 36.3 +/- 7.6 units at 25 and 32 degrees C, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Salt loads attenuate potassium-induced vasodilation of forearm vasculature in humans.

To evaluate the role of the sodium pump in resistance control in vivo, we studied vascular responses to potassium, which produces vasodilation by the activation of vascular Na+, K(+)-ATPase, in normotensive volunteers receiving a high salt diet compared with volume-depleted subjects receiving diuretic treatment. Forearm blood flow was measured by strain-gauge plethysmography during small increments in local concentrations of potassium with intrabrachial arterial infusions of KCl. Infusions of 0.12 and 0.24 mEq/min KCl increased forearm blood flow and decreased forearm vascular resistance in a dose-dependent fashion. But the simultaneous intrabrachial arterial infusion of 2 micrograms/min ouabain, a Na+,K(+)-ATPase inhibitor, could blunt the decremental response of vascular resistance to 0.12 mEq/min KCl. The decrements of vascular resistance with KCl infusions divided by the initial resistance were significantly less with ouabain compared with those without ouabain (43 +/- 4% versus 57 +/- 3%, p < 0.01). This suggests that potassium produces vasodilation by the activation of vascular Na+,K(+)-ATPase activity. Similarly, salt loading (180 mEq NaCl for 7 days) after treatment with diuretics could attenuate percent decrements of resistance with KCl infusions (39 +/- 3% versus 53 +/- 2%, p < 0.01), whereas vascular resistance responses to sodium nitroprusside, a nonspecific vasodilator, and to verapamil, a calcium antagonist, did not change with salt loading after volume depletion. Therefore, salt loading could attenuate forearm vascular response to potassium specifically, as did the administration of ouabain.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of captopril on the superior mesenteric artery and portal venous blood flow in normal man.

1. Measurements of superior mesenteric artery and portal venous blood flow were made non-invasively along with systemic and other regional (cardiac index, forearm and cutaneous blood flow) vascular responses to acute ingestion of the ACE inhibitor captopril (50 mg) or placebo (50 mg vitamin C), in 12 healthy subjects while supine and during head-up tilt. 2. After captopril, superior mesenteric artery and portal blood flow rose markedly with a reduction in superior mesenteric artery vascular resistance. Supine blood pressure was unchanged but cardiac index and forearm blood flow rose; during head-up tilt, blood pressure fell in some subjects. 3. There was a rise in levels of plasma renin activity and a fall in levels of plasma angiotensin II after captopril. After placebo, there were no significant changes in splanchnic blood flow, systemic or other regional responses and in biochemical measurements, while supine. 4. Our studies indicate that captopril is a potent dilator of the splanchnic vascular bed and suggest that this action may contribute to its therapeutic effects. The studies indicate a role for angiotensin II in the control of this large vascular bed although other agents (bradykinin, prostacyclin) may contribute.

Assessment of autonomic function in patients with neurally mediated syncope: Augmented cardiopulmonary baroreceptor responses to graded orthostatic stress

Objectives. The purpose of this study was to assess vagal tone and cardiopulmonary baroreceptor activity in patients with tiltinduced neurally mediated syncope.Background. The causes of individual susceptibility to orthostatic stress leading to recurrent neurally mediated syncope remain obscure. The trigger for sympathetic withdrawal and increased vagal activity is believed to be stimulation of ventricular mechanoreceptors.Methods. Seventeen patients (mean age 50.6 years) with recurrent syncope and a positive response on a 45-min 60 ° bead-up tilt test were compared with a control group of 17 patients (mean age 47.5 years) with unexplained syncope und negative tilt test findings. Vagal activity was assessed by high pressure baroreceptor testing and by temporal and spectral analysis of heart rate variability during Holter ambulatory electrocardiographic monitoring. Cardiopulmonary baroreceptor sensitivity was assessed by measurement of forearm vascular responses to lower body negative pressure.Results. Mean high pressure baroreceptor sensitivity was 16.4 ± 12.2 ms/mm Hg in the group with a positive tilt test response compared with 15.1 ± 13.0 ms/mm Hg in the control group (p = NS). There were no agnificant differences between the groups in any of the temporal or spectral measures of heart rate variability. The increase to forearm vascular résistance in response to lower body negative pressure was 11.5 ± 14.2 U in patents with tilt-inducetd syncope and 3.5 ± 3.2 U in the control group at -5 mm Hg, 16.8 ± 18.6 U and 4.8 ± 5.3 U, respectively, at -10 mm Hg and 26.4 ± 24.3 U and 10.2 ± 7.8 U, respectively, at -20 mm Hg (p < 0.001).Concisions. Patients with tilt-induced neurally mediated syncope have augmented cardiopulmonary baroreceptor responses to orthostatic stress. This finding sheds new light on the etiology of neurally mediated syncope.

Paradoxical forearm vasodilatation and haemodynamic improvement during cardiopulmonary baroreceptor unloading in patients with congestive heart failure

1. To examine the contribution of paradoxical reflex forearm vasodilatation during unloading of cardiopulmonary baroreceptors to systemic haemodynamics, the responses of central and peripheral haemodynamics during lower-body negative pressure were measured in 24 patients with chronic congestive heart failure (New York Heart Association functional class II-IV) and were compared with those of 10 normal subjects. 2. Lower-body negative pressure of less than -20 mmHg caused a significant forearm vasoconstriction in normal subjects but not in patients with congestive heart failure. In the individual cases, however, eight patients (subgroup A) had a significant forearm vasoconstriction, whereas 10 patients (subgroup B) had a paradoxical forearm vasodilatation. The remaining six patients had a blunted forearm vascular response. Baseline pulmonary capillary wedge pressure (26 +/- 3 versus 20 +/- 1 mmHg, means +/- SEM) and left ventricular wall stress in end-diastole (57 +/- 6 versus 37 +/- 4 g/cm2) were significantly (P < 0.05) higher in subgroup B than in subgroup A. 3. During lower-body negative pressure of -20 mmHg, the plasma level of noradrenaline, systemic vascular resistance and cardiac index did not change significantly in subgroup A. In subgroup B, however, during this orthostatic stimulus systemic vascular resistance fell significantly from a baseline value of 2023 +/- 109 to 1740 +/- 110 dyn s-1 cm-5 (P < 0.01) and cardiac index increased significantly from a baseline value of 2.0 +/- 0.1 to 2.5 +/- 0.2 1 min-1 m-2 (P < 0.01) despite there being no significant change in the plasma level of noradrenaline. 4. After treatment, a second bout of lower-body negative pressure was applied to seven patients in subgroup B. The forearm vascular response to the second bout of lower-body negative pressure was normalized. 5. These data suggest that the patients with more severe heart failure show a paradoxical forearm vasodilatation during mild lower-body negative pressure and that this altered cardiopulmonary baroreflex control of the circulation serves to improve the depressed cardiac performance.

Étude des baroréflexes à haute et basse pressions dans l'intérolérance orthostatique après simulation d'apesanteur

Weightlessness produces orthostatic intolerance. We studied cardiopulmonar and arterial baroreflexes through non-invasive methods following -5 head down bed rest on 20 volunteers. Dissociated cardiovascular responses to LBNP-40mmHg were observed. Forearm vascular and heart rate responses were unmodified, following LBNP-5, -10, -15mmHg and neck chamber test, suggesting an alteration of baroreflexes systems interrelation.

Effect of omega-3 fatty acids on the vascular response to angiotensin in normotensive men

There is a widespread interest in fish oil as a dietary supplement and possible nonpharmacologic adjunct in the treatment of hypertension. The effect of dietary fish oil on blood pressure is controversial and the effect on systemic hemodynamics and regional vascular reactivity in humans is unknown. To address these questions, a doubleblind, placebo-controlled, crossover study on the effect of dietary fish oil substitution was performed during a carefully controlled diet in 8 normotensive men. Systemic hemodynamics and the forearm vascular response to intrabrachial artery infusions of norepinephrine, phentolamine and angiotensin II were obtained. Compared with a safflower oil placebo, dietary fish oil had no effect on cardiac output (6.42 ± 0.38 vs 6.87 ± 0.28 liters/ min, p = not significant) or 24-hour blood pressure (122/68 ± 3/3 vs 122/68 ± 3/2 mm Hg, p = not significant). The vascular response to norepinephrine and phentolamine was unchanged. Fish oil, however, significantly (p < 0.05) reduced forearm vascular resistance responses to angiotensin II. These changes were associated with a reduction in plasma triglycerides (64 ± 9 vs 39 ± 4 mg/dl, p = 0.02) and an increase in plasma eicosapentaenoic acid levels (0.51 ± 0.25 vs 1.72 ± 0.35 μM, p < 0.05). Substitution of a moderate dose of fish oil for fat in a “Western diet” selectively attenuates the vascular response to angiotensin independently of changes in α-adrenergic vasoconstriction or systemic hemodynamics.

Glucocorticoid-dependent hypertension

Glucocorticoid (GC) excess (Cushing's syndrome) is associated with hypertension in at least 70% of patients (in our series 89/130), independently of the subtype (pituitary or adrenal) and the duration, but not of the age of the patients. Cardiovascular damage is quite frequent in hypertensives, but is sometimes also present in normotensives. The mortality of patients with Cushing's syndrome is four times that of the general population when matched for age and sex, and much of this excess mortality is caused by cardiovascular disease. Hypertension remits in most of the patients after successful treatment, but may persist in some. Hypertension also occurs in 20% of patients treated with GC orally. The type of hypertension is independent of salt uptake, can not be controlled by spironolactone but is inhibited by a GC antagonist such as RU486. Experimentally-induced hypertension with oral cortisol (F) is associated with a rise in cardiac output, a fall in calculated total peripheral resistance, an increased forearm vascular responsiveness to exogenous norepinephrine, but no change in overall sympathetic tone, or in norepinephrine reuptake. The increased pressor responsiveness is probably due to local postsynaptic effector mechanisms in the resistance vessels, which could be important in phasic increases in neuronally mediated constrictor responses. Both in patients with Cushing's syndrome and in those on chronic GC treatment, the circadian blood pressure variations are absent or reversed. This may contribute to the deleterious effects of the GC excess on blood vessels. The vascular effects of the GC may be mediated by the activation of specific cardiovascular receptors, by modulating vascular transport systems, or by altered catecholamine or prostaglandin metabolism. GC may also act as mineralocorticoids (MC): in fact type 1 MC receptors are unable, in vitro, to distinguish between aldosterone and cortisol. The specificity-conferring mechanism of typical target organs for MC (e.g. kidney)—is thought to be due to the action of local 11-β-hydroxysteroid dehydrogenase, which converts F to biologically inactive cortisone (E). When the activity of the enzyme is impaired (syndrome of apparent MC excess, liquorice or carbenoxolone administration), F acts as a MC and MC-hypertension with hypokalemia occurs. Furthermore, in the syndrome of dexamethasone-suppressible hyperaldosteronism, an abnormal elevation of 18-hydroxy- or 18-oxo-F (possibly as a consequence of gene conversion between the 2 genes which encode for 11-β-hydroxylase in the zona fasiculata and glomerulosa, respectively) may contribute to the circulating MC activity, that results higher than expected by the measured levels of aldosterone, deoxycorticosterone and F.

The long-term reproducibility of clinical tests of autonomic cardiovascular function in normal man.

Tests for the integrity of autonomic cardiovascular reflexes have been widely used in the clinic and in space physiology for decades. However, whereas some information on the short-term reproducibility of such tests are available, little is known about their long-term reproducibility. The work in this study was, therefore, directed towards assessing intra- and inter-subject variations in responses (heart rate, mean arterial blood pressure, forearm blood flow and forearm vascular conductance) to cortical arousal, cold face stimulation and lower body negative pressure (at 10, 30 and 50 mmHg) in eleven healthy male subjects (aged between 22 and 45 years). Subjects were studied repeatedly (each month) over a 6-month period. It was found that forearm vascular conductance responses to cold face stimulation were the most reproducible (mean coefficient of variation 10.9%), and with diminishing reproducibility curve responses to lower body negative pressure at 50 mmHg (mean coefficient of variation 12.4%), lower body negative pressure at 30 mmHg (mean coefficient of variation 18.9%), lower body negative pressure at 10 mmHg (mean coefficient of variation 28.0%), and responses to cortical arousal (mean coefficient of variation 39.6%). Generally, subjects who showed the largest responses to cold face stimulation also showed the largest responses to the other tests, and vice versa. It is concluded that there is intra-individual variability in the responsiveness and reproducibility of cardiovascular tests and that the cardiovascular responses to cold face stimulation and lower body negative pressure at 50 mmHg are the most reproducible.

Pressor responsiveness in corticosteroid-induced hypertension in humans.

In previous studies short-term cortisol increased cold pressor responses and the rise in forearm vascular resistance accompanying intra-arterial norepinephrine without an increase in overall resting sympathetic nervous activity. The present study examined whether these alterations in pressor response are glucocorticoid or mineralocorticoid effects, or both. Normal male subjects (n = 12) received either fludrocortisone, 0.3 mg daily (n = 6), or dexamethasone, 3 mg daily (n = 6), for 7 days. Hemodynamic studies were performed before and on day 7 of treatment. Fludrocortisone increased body weight from 69.3 +/- 1.8 to 71.1 +/- 2 kg (p less than 0.001), cardiac output from 5.0 to 6.0 l/min (+/- 0.1, p less than 0.01), mean arterial pressure from 82 +/- 1 to 91 +/- 1 mm Hg (p less than 0.001), cold pressor responsiveness from 13.0 to 39.0 mm Hg/ml per 100 ml per minute (R units) (+/- 4.3, p less than 0.01), and forearm vascular response to intra-arterial norepinephrine (F = 59.4, p less than 0.01) and angiotensin II (F = 30.8, p less than 0.01) infusions. Total peripheral resistance fell from 22.0 to 20.1 mm Hg/l per minute (+/- 0.3, p less than 0.05). Dexamethasone did not increase cardiac output, 5.1 to 5.2 l/min (+/- 0.1), or body weight but did increase mean arterial pressure from 82 +/- 3 to 91 +/- 3 mm Hg (p less than 0.001), cold pressor responsiveness from 8.6 to 17.1 R units (+/- 2.8, p less than 0.05), and forearm vascular response to intra-arterial norepinephrine (F = 33.0, p less than 0.01) and angiotensin II (F = 54.9, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Interactions between atrial natriuretic factor and the autonomic nervous system

In addition to its natriuretic, hormonal and vascular actions, atrial natriuretic factor (ANF) may interact importantly with the function of the autonomic nervous system. It has been hypothesized that ANF may exert its cardiovascular and possibly renal effects by interfering with autonomic control mechanisms. In, animal experiments the hypotension that is caused by ANF is usually not associated with the expected reflex tachycardia or increased efferent sympathetic activity. Furthermore, bilateral vagotomy can attenuate the hypotensive action of ANF which suggest that ANF may stimulate sympathoinhibitory afferent vagal activity from the cardiopulmonary baroreceptor system. In man, ANF may alter reflexogenic-mediated forearm vascular responses to cardiopulmonary deactivation which suggest that ANF may have an important role as a neuromodulator of autonomic nervous function, a role that could serve to amplify or facilitate the peripheral hormonal actions of ANF. This neuromodulating influence of ANF could be due to several mechanisms: it could modulate baroreflex mechanisms or it could have direct effects on autonomic centres in the brain or it could have effects on peripheral neurotransmission. The role of the autonomic nervous system in modulating the release of ANF remains controversial. Finally, there is growing evidence to suggest that there is a reciprocal interplay between ANF and the sympathetic nervous system in peripheral target tissues which may have important pathophysiological significance.