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PubMed1994

Differential reflex control of forearm and calf resistance vessels by chemosensitive cardiac afferent activation.

The aim of this study was to determine whether chemosensitive ventricular afferent activation in humans evokes a diffuse pattern of reflex vasodilation involving the skeletal muscle circulation of all the extremities or a highly specified pattern of vasodilation that is limited to the rather small vascular bed of the forearm. In 10 patients with innervated ventricles and 7 patients with denervated ventricles resulting from heart transplantation, we performed simultaneous plethysmographic recordings of blood flow in the forearm and calf during chemosensitive ventricular afferent activation with intracoronary Renografin. In patients with innervated ventricles, intracoronary Renografin evoked directionally opposite vascular responses in the forearm and calf: forearm resistance decreased from 50 +/- 11 to 31 +/- 8 units, whereas calf resistance increased from 42 +/- 7 to 59 +/- 9 units (P < 0.05, calf vs. forearm). Forearm vasodilation was eliminated after heart transplantation, indicating that this is a reflex response caused by ventricular afferents. In contrast, calf vasoconstriction was well preserved despite ventricular deafferentation, indicating that this response is caused by mechanisms other than ventricular afferent activation, possibly the sinoaortic baroreceptors. Taken together, these findings document a remarkable degree of specificity in the effects of cardiac afferent activation on the reflex regulation of regional vasomotor tone in humans.

Adult↗
PubMed1996

Contribution of nitric oxide and prostaglandins to reactive hyperemia in human forearm.

We investigated the separate and combined contributions of nitric oxide (NO) and vasodilating prostaglandins as mediators of reactive hyperemia in the human forearm. Forearm blood flow (FBF) was measured with venous occlusion plethysmography after 5 min of ischemia. In one protocol (n = 12), measurements were made before and after intra-arterial administration of the NO synthase inhibitor NG-monomethyl-L-arginine (L-NMMA) to one forearm. In a separate protocol (n = 7), measurements were made before and after systemic administration of the cyclooxygenase inhibitor ibuprofen and again after L-NMMA. L-NMMA reduced baseline FBF at rest (2.7 +/- 0.4 to 1.6 +/- 0.2 ml.100 ml-1.min-1; P < 0.05) and had a modest effect on peak forearm vascular conductance and flow (forearm vascular conductance = 31.1 +/- 3.1 vs. 25.7 +/- 2.5 ml.min-1.100 ml forearm-1.100 mmHg of perfusion pressure-1.min-1, P < 0.05; FBF = 26.6 +/- 2.9 vs. 22.8 +/- 2.6 ml.100 ml-1.min-1, P = 0.055). Total excess flow above baseline during reactive hyperemia was unaffected by L-NMMA (14.3 +/- 3.0 vs. 13.1 +/- 2.4 ml/100 ml; P < 0.05). Ibuprofen did not change FBF at rest, reduced peak FBF from 27.6 +/- 1.9 to 20.3 +/- 2.7 ml.100 ml-1.min-1 (P < 0.05), but had no effect on total excess flow above baseline, Infusion of L-NMMA after ibuprofen reduced FBF at rest by 40%, had no effect on peak flow, but reduced total excess flow above baseline from 12.0 +/- 2.5 to 7.6 +/- 1.3 ml/100 ml (P < 0.05). These date demonstrate that NO synthase inhibition has a modest effect on peak vasodilation during reactive hyperemia but plays a minimal role later. Prostaglandins appear to be important determinants of peak flow. The effects of NO synthase inhibition during reactive hyperemia may also be potentiated by concurrent cyclooxygenase inhibition.

Adolescent↗
PubMed2002

Aging and forearm postjunctional alpha-adrenergic vasoconstriction in healthy men.

BACKGROUND: Muscle sympathetic vasoconstrictor nerve activity increases with age in healthy humans but does not result in an augmented forearm vasoconstrictor tone. We tested the hypothesis that this is due to a reduction in postjunctional alpha-adrenergic responsiveness to endogenous norepinephrine (NE) release and determined whether this was specific to alpha1- or alpha2-adrenergic receptors. METHODS AND RESULTS: Forearm blood flow (FBF, by strain-gauge plethysmography) responses to local intra-arterial infusions of tyramine (which evokes endogenous NE release), phenylephrine (selective alpha1-agonist), and clonidine (alpha2-agonist) were determined in 10 young (aged 26+/-1 [mean+/-SEM] years) and 10 older (aged 65+/-1 years) healthy normotensive men after local beta-adrenergic blockade with propranolol. Basal forearm vascular tone was not different in young men and older men. The percentage reduction in FBF in response to the highest dose of tyramine was blunted in older men compared with young men (-37+/-3% versus -49+/-3%, respectively; P<0.01) despite a greater increase in deep venous NE concentration in older men (910+/-103 versus 565+/-69 pg/mL, respectively; P<0.001). Maximal reductions in FBF to phenylephrine were also blunted in older men (-47+/-2% versus -58+/-3% in young men, P<0.05). In contrast, the reductions in FBF (-36+/-7% versus -40+/-3% for older versus young men, respectively) and also in venous NE concentration (-79+/-24 versus -84+/-13 pg/mL for older versus young men, respectively) to clonidine were similar in the 2 groups. Finally, forearm sympathetic alpha-adrenergic vasoconstrictor tone (assessed via nonselective alpha-blockade with phentolamine) was significantly lower in older men. CONCLUSIONS: Our results indicate that human aging is associated with a reduction in forearm postjunctional alpha-adrenergic responsiveness to endogenous NE release and that this might be specific to alpha1-adrenergic receptors. Furthermore, the contribution of sympathetic alpha-adrenergic vasoconstriction to basal forearm vascular tone is reduced with age in healthy men.

Adrenergic Agonists↗
PubMed2001

The phytoestrogen genistein produces acute nitric oxide-dependent dilation of human forearm vasculature with similar potency to 17beta-estradiol.

BACKGROUND: Genistein, a phytoestrogen, may have estrogenic cardioprotective actions. We investigated whether genistein influences endothelium-dependent vasodilation in forearm vasculature of healthy human subjects and compared the effects of genistein with those of 17beta-estradiol. METHODS AND RESULTS: The brachial arterial was cannulated with a 27-gauge needle for drug infusion. Forearm blood flow responses were measured with strain-gauge plethysmography. Genistein (10 to 300 nmol/min, each dose for 6 minutes) produced a dose-dependent increase in forearm blood flow from 3.4+/-0.3 to 9.6+/-1.3 mL x min(-1) x 100 mL forearm(-1) (mean+/-SEM) in men (n=9, P:<0.0001 by ANOVA). The mean forearm venous concentration of genistein during infusion of the highest dose was 1.8+/-0.3 micromol/L in 6 additional men. Genistein produced a similar increase in blood flow in premenopausal women. Daidzein, another phytoestrogen, was ineffective, but equimolar concentrations of 17beta-estradiol caused similar vasodilation to genistein. Responses to genistein and 17beta-estradiol were inhibited to the same degree by the NO synthase inhibitor N:(G)-monomethyl-L-arginine. A threshold dose of genistein potentiated the endothelium-dependent vasodilator acetylcholine but not the endothelium-independent vasodilator nitroprusside. CONCLUSIONS: Genistein causes L-arginine/NO-dependent vasodilation in forearm vasculature of human subjects with similar potency to 17beta-estradiol and potentiates endothelium-dependent vasodilation to acetylcholine.

Acetylcholine↗
PubMed1985

Increased forearm vascular reactivity in patients with hypertension after repair of coarctation.

To determine whether altered vascular reactivity could contribute to hypertension after repair of coarctation, the change in forearm and calf vascular resistances to small intra-arterial infusions of norepinephrine were measured in six patients who had undergone surgical correction of coarctation of the aorta but still had upper extremity hypertension and compared with similar measurements made in five normotensive patients with mild heart disease. Only the mean upper extremity pressure was significantly greater in the group that underwent repair of coarctation (102 +/- 11 vs 83 +/- 5 mm Hg, p less than .05, for mean arm pressures and 96 +/- 13 vs 83 +/- 7 mm Hg for mean leg pressures in patients who had coarctation vs normotensive patients, respectively). Forearm and calf blood flows were measured in the right arm and leg with a mercury-in-plastic strain-gauge plethysmograph. Forearm and calf vascular resistances were calculated by dividing mean arterial pressure of the appropriate extremity by the blood flow of that extremity. Norepinephrine was infused into the right brachial and femoral arteries of the patients at doses of 0.02, 0.05, 0.1, 0.2, 0.3, 0.5, and 0.7 microgram/min. Resting forearm and calf vascular resistances were similar in both groups of patients. The norepinephrine dose-response curves showed that control patients required more than three times the norepinephrine to produce the same percent increase in forearm vascular resistance (after 0.2 microgram/min forearm vascular resistance increased by 55% in the coarctation group, while the resistance in the control group increased by only 3%, p less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1987

Enhanced forearm blood flow during mental stress in children of hypertensive parents.

This study compared changes in forearm blood flow, forearm vascular resistance, blood pressure, and heart rate elicited by mental stress (mental arithmetic) in 12 adolescents with a hypertensive parent and 13 age-matched adolescents with normotensive parents. The two groups did not differ in resting forearm blood flow, forearm vascular resistance, heart rate, or blood pressure. During mental stress, children with a family history of hypertension had a significantly greater increase in forearm blood flow than did children of normotensive parents (+37.5 +/- 8.0 vs +12.8 +/- 7.5%; p less than 0.05) and a trend toward reduced forearm vascular resistance (p = 0.08). Mental stress significantly increased systolic blood pressure (p less than 0.0001), diastolic blood pressure (p less than 0.001), and heart rate (p less than 0.03) in both groups. The blood pressure and heart rate responses to stress were not significantly different between groups. There was no evidence of a prolonged response or a different pattern of recovery in children with a family history of hypertension. This study indicates that regional blood flow responses underlying similar blood pressure increases during mental stress may be different in adolescents with and without a family history of hypertension.

Adolescent↗
PubMed1992

Resting and maximal forearm skin blood flows are reduced in hypertension.

To find whether the vasodilator capacity of nonacral skin is reduced in hypertension, we measured forearm blood flow by venous occlusion plethysmography in 10 seated normotensive (mean +/- SD mean arterial pressure, 94 +/- 5 mm Hg) and 10 hypertensive (112 +/- 9 mm Hg) men at rest for 39 minutes while the forearm was heated with water at 42 degrees C, a maneuver known to selectively and maximally vasodilate skin. Blood pressure, measured every 5 minutes, did not change with heating. We found that in the normotensive group resting forearm blood flow was higher (3.64 +/- 1.12 versus 2.48 +/- 0.58 ml/100 ml tissue per minute, p less than 0.001; normotensive group versus hypertensive group) and resting forearm vascular resistance lower (30.17 +/- 10.99 versus 48.88 +/- 17.37 mm Hg.min.100 ml tissue per minute, p less than 0.05; normotensive group versus hypertensive group), and maximal forearm blood flow with local heating was higher (29.32 +/- 11.99 versus 18.19 +/- 4.50 ml/100 tissue per minute, p less than 0.018; normotensive group versus hypertensive group and vascular resistance lower (4.07 +/- 1.04 versus 6.54 +/- 1.17 mm Hg.min.100 ml tissue per minute, p less than 0.005; normotensive group versus hypertensive group). To find whether this degree and duration of local warming maximally vasodilated the skin in hypertensive subjects (as it does in normotensive subjects), we measured forearm skin blood flow before and during local heating plus 10 minutes of ischemia using a laser Doppler flowmeter.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Reflex sympathetic activation induces acute insulin resistance in the human forearm.

Inferences about the association between sympathetic overactivity and insulin resistance have been drawn from the infusion of sympathomimetic amines in supraphysiological doses. We used the isolated perfused human forearm to investigate the effect of reflex-induced sympathetic nervous system activation on the peripheral utilization of glucose in the skeletal muscles of 14 healthy men. Local hyperinsulinemia in the forearm (132 +/- 25 microunits/mL for 90 minutes) induced a significant increase in the utilization of glucose from baseline (16.4 +/- 3.1 mg.dL-1.min-1 per 100 mL forearm volume) to a plateau (85.7 +/- 15.1 mg.dL-1.min-1 per 100 mL forearm volume) between 40 and 60 minutes of insulin infusion but did not alter the utilization of oxygen. Reflex sympathetic nervous system activation was elicited by unloading of cardiopulmonary receptors with bilateral thigh cuff inflation to 40 mm Hg between 60 and 90 minutes of insulin infusion. Blood flow in the forearm was significantly decreased with inflation of thigh cuffs (average decrease of 19%, p < 0.0001). As a result of thigh cuff inflation, there was a reduction in the utilization of glucose (a decrease of 23%, p < 0.02), whereas oxygen utilization was unchanged. We find that an increase in sympathetic nervous system activation (within the normal range of physiological responses) can cause acute insulin resistance in the forearm of healthy volunteers. The reflex caused no change in oxygen utilization, but the same stimulus elicited a decrease in the utilization of glucose.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Effects of insulin on vascular responses to mental stress and norepinephrine in human forearm.

Essential hypertension is frequently associated with insulin resistance and hyperinsulinemia. In vitro, insulin has vasodilator actions, but its possible hemodynamic effect on muscular vascular beds in humans is a matter of controversy. We investigated the effects of local hyperinsulinemia on the vascular responses to norepinephrine and physiological vasodilation during mental stress in the perfused-forearm model. Nine glucose-tolerant, normotensive, nonobese men (aged 22 to 36 years) participated. Forearm perfusion studies (venous occlusion plethysmography) were performed during randomized, double-blind intrabrachial artery infusions of insulin (to raise plasma insulin 100 microU/mL) or placebo for 2 hours. A mental stress test and stepwise intra-arterial infusion of norepinephrine (6 to 1200 ng/min) were performed during each infusion. Insulin infusion increased venous plasma insulin to 98.4 microU/mL and increased net glucose uptake threefold. Insulin had a gradual vasodilator effect (P < .05 by ANOVA), and after 90 minutes blood flow was 36 percent units higher relative to the control arm than during placebo (P = .005). During mental stress, forearm blood flow increased by 81% (t test, P = .006) and 92% (P = .01) in the study arm during insulin and placebo infusions, respectively (insulin versus placebo, P = NS). An increased forearm blood flow was maintained throughout the mental stress test during insulin infusion (ANOVA, P = .03). Forearm glucose uptake increased during stress, reflecting forearm hyperperfusion since fractional glucose extraction was unaffected by stress. The increased blood flow was maintained throughout the five norepinephrine dose steps (ANOVA, P < .04).(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Vessels↗
PubMed1997

Norepinephrine release in the human forearm: effects of epinephrine.

It has been postulated that delayed facilitation of norepinephrine release by epinephrine is causally related to the development of hypertension. It has been proposed that a brief increase in epinephrine concentrations results in the uptake of epinephrine into the sympathetic nerve terminal. Subsequent rerelease of epinephrine stimulates presynaptic beta-adrenergic receptors, resulting in a prolonged increase in plasma norepinephrine (NE) concentrations, with amplified sympathetic responses and vasoconstriction. To determine whether such epinephrine-induced, delayed facilitation of NE release occurs in a vascular bed draining resistance vessels and, if it occurs, whether that facilitation differs in hypertension, we used a radioisotope dilution method to measure unstimulated and isoproterenol-stimulated forearm NE spillover before, during, and after a 50 ng/min infusion of epinephrine for 30 minutes directly into the brachial artery. No delayed facilitatory effects of epinephrine on forearm NE spillover were observed in either 6 normotensive (NT) or 8 borderline hypertensive (BHT) subjects (NT unstimulated forearm NE spillover preepinephrine 1.79+/-0.41 ng/min versus postepinephrine 2.36+/-0.65 ng/min, P=.38; BHT preepinephrine 2.24+/-0.70 ng/min versus postepinephrine 1.93+/-0.46 ng/min, P=.51; NT isoproterenol-stimulated forearm NE spillover preepinephrine 4.61+/-1.01 ng/min versus postepinephrine 4.4+/-0.98 ng/min, P=.9; BHT preepinephrine 4.04+/-1.36 ng/min versus postepinephrine 4.69+/-1.49 ng/min P=.5). We conclude that the short-term local infusion of epinephrine does not have a delayed facilitatory effect on forearm NE spillover in NT or BHT subjects. Therefore, the prolonged increase in NE concentrations after epinephrine infusion previously shown systemically, and not seen locally in the forearm, suggests that the delayed facilitatory response to epinephrine may occur in other organs.

Adult↗
PubMed2000

Functional importance of angiotensin-converting enzyme-dependent in situ angiotensin II generation in the human forearm.

To assess the importance for vasoconstriction of in situ angiotensin (Ang) II generation, as opposed to Ang II delivery via the circulation, we determined forearm vasoconstriction in response to Ang I (0.1 to 10 ng. kg(-1). min(-1)) and Ang II (0.1 to 5 ng. kg(-1). min(-1)) in 14 normotensive male volunteers (age 18 to 67 years). Changes in forearm blood flow (FBF) were registered with venous occlusion plethysmography. Arterial and venous blood samples were collected under steady-state conditions to quantify forearm fractional Ang I-to-II conversion. Ang I and II exerted the same maximal effect (mean+/-SEM 71+/-4% and 75+/-4% decrease in FBF, respectively), with similar potencies (mean EC(50) [range] 5.6 [0.30 to 12.0] nmol/L for Ang I and 3.6 [0.37 to 7.1] nmol/L for Ang II). Forearm fractional Ang I-to-II conversion was 36% (range 18% to 57%). The angiotensin-converting enzyme (ACE) inhibitor enalaprilat (80 ng. kg(-1). min(-1)) inhibited the contractile effects of Ang I and reduced fractional conversion to 1% (0.1% to 8%), thereby excluding a role for Ang I-to-II converting enzymes other than ACE (eg, chymase). The Ang II type 1 receptor antagonist losartan (3 mg. kg(-1). min(-1)) inhibited the vasoconstrictor effects of Ang II. In conclusion, the similar potencies of Ang I and II in the forearm, combined with the fact that only one third of arterially delivered Ang I is converted to Ang II, suggest that in situ-generated Ang II is more important for vasoconstriction than circulating Ang II. Local Ang II generation in the forearm depends on ACE exclusively and results in vasoconstriction via Ang II type 1 receptors.

Adolescent↗
PubMed2000

Bradykinin-induced vasodilation of human forearm resistance vessels is primarily mediated by endothelium-dependent hyperpolarization.

Bradykinin (BK) stimulates endothelial cells to release a number of relaxing factors, such as NO, prostanoids (PGs), and an endothelium-derived hyperpolarizing factor (EDHF). However, the contributions of NO, PG, and EDHF in the vascular relaxation to BK vary with species and anatomic origin of blood vessels used. Therefore, the present study was designed to investigate the contributions of NO, PG, and EDHF in vasodilation caused by BK in human forearm resistance vessels. Forearm blood flow (FBF) was recorded with venous occlusion plethysmography in healthy nonsmoking subjects. At first, studies were performed to validate the NO clamp technique for its ability to inhibit endogenous NO generation. Brachial artery infusion of serotonin (0.6, 1.8, and 6 ng. 100 mL forearm volume [FAV](-1). min(-1)) caused significant forearm vasodilation (2.6 to 4.6 mL. 100 mL FAV(-1). min(-1)), which is known to be NO mediated. Indeed, during the NO clamp, cumulative doses of serotonin caused no vasodilation (2.4 to 2.6 mL. 100 mL FAV(-1). min(-1)), indicating that the generation of endogenous NO was completely blocked. Thereafter, the vasodilative actions of BK were investigated. Brachial artery infusion of BK (50, 100, and 200 ng. 100 mL FAV(-1). min(-1)) caused significant forearm vasodilation in all studies (from 3.1 to 20.4 mL. 100 mL FAV(-1). min(-1)). After the inhibition of cyclooxygenase and NO synthase activity through the use of aspirin and the NO-clamp technique, BK increased FBF in a similar manner (3.9 to 18.9 mL. 100 mL FAV(-1). min(-1)), indicating that the vasodilative actions of BK are independent of NO and PG generation. However, vasodilation caused by the 2 lower doses of BK were significantly attenuated after K(Ca) channel activity was blocked with tetraethylammonium chloride (0.1 mg. 100 mL FAV(-1). min(-1)), suggesting that in the lower dose range, BK mediates vasodilation through the opening of vascular potassium channels. In conclusion, BK is a potent vasodilator peptide in human forearm resistance vessels, causing vasodilation through hyperpolarization of the vascular wall independent of NO and PG production. In addition, the NO-clamp technique is a valid instrument to investigate the contribution of NO in the vasodilative response to different agents.

Adolescent↗
PubMed1991

Regulation of forearm lipolysis in different types of obesity. In vivo evidence for adipocyte heterogeneity.

UNLABELLED: Forearm and systemic adipose tissue free fatty acid (FFA) release was measured in eight nonobese, six lower-body obese, and eight upper-body obese women under basal, hyperinsulinemic, and hypoinsulinemic conditions to determine whether forearm fat is regulated in a similar manner as whole body fat. RESULTS: Adipose tissue palmitate release was greater from forearm than whole body (5.97 +/- 0.75 vs. 3.84 +/- 0.34 mumol.kg fat-1.min-1, respectively, P less than 0.005, n = 22 subjects). Systemic palmitate release, relative to fat mass, was significantly (P less than 0.01) greater in nonobese than upper-body obese, and upper-body obese than lower-body obese women, and forearm adipose tissue palmitate release followed the same pattern. Hyperinsulinemia suppressed systemic and forearm lipolysis to similar degrees, however, hypoinsulinemia consistently increased systemic palmitate flux without increasing forearm palmitate release. These results confirm the heterogeneity of adipose tissue in an in vivo model and emphasize the need to consider which adipose tissue depots are responsible for the differences in systemic FFA flux in obese and nonobese humans.

Adipose Tissue↗
PubMed1998

Vasodilatory capacity of forearm resistance vessels is augmented in hypercholesterolemic patients after treatment with fluvastatin.

Atherosclerotic vessels are characterized by endothelial and structural abnormalities as indicated by an impaired vasodilation to metabolic requirements. To determine whether effective treatment of hypercholesterolemia may improve vasodilatory capacity of resistance vessels, the authors examined the impact of 12 and 24 weeks of lipid-lowering therapy with the hepatic hydroxymethylglutaryl coenzyme A (HMG-CoA)-reductase inhibitor fluvastatin (40 to 80 mg/day) on the increment in forearm blood flow during reactive hyperemia in 24 hypercholesterolemic patients (mean age: 56 +/- 11 years; 15 men/9 women). Changes in forearm blood flow in response to reactive hyperemia were measured by venous occlusion plethysmography. Serum low-density lipoprotein (LDL)-cholesterol fell from 213 +/- 32 to 125 +/- 27 mg/dL (P<0.001) after 12 weeks and remained stable at a level of 125 +/- 18 mg/dL after 24 weeks of treatment. Baseline forearm blood flow was similar before and after 12 and 24 weeks of therapy. In contrast, forearm blood flow at peak reactive hyperemia was greater at week 12 (37.0 +/- 22.9 mL/min/100 mL; P<0.05), and at week 24 (47.1 +/- 33.5 mL/min/100 mL; P<0.05) than at week 0 (30.5 +/- 18.1 mL/min/100 mL). Compared with week 0 (defined as 100%), the percent change in forearm blood flow in response to reactive hyperemia was augmented at week 12 (171 +/- 144%; P<0.05 vs week 0) and at week 24 (218 +/- 228%; P<0.05 vs week 0). Thus, the lowering of high serum LDL cholesterol after short-term treatment with fluvastatin increased the blood flow responses during reactive hyperemia in forearm resistance vessels. These data indicate a beneficial effect of HMG-CoA reductase inhibition on structural wall properties of peripheral arteries in human atherosclerosis.

Aged↗
PubMed1988

Quantitation of forearm glucose and free fatty acid (FFA) disposal in normal subjects and type II diabetic patients: evidence against an essential role for FFA in the pathogenesis of insulin resistance.

This study was designed to quantitate glucose and FFA disposal by muscle tissue in patients with type II diabetes and to investigate the relationship between FFA metabolism and insulin resistance. The forearm perfusion technique was used in six normal subjects and two groups of normal weight diabetic patients, i.e. untreated (n = 8) and insulin-treated (n = 6). The latter received 2 weeks of intensive insulin therapy before the study. Plasma insulin levels were raised acutely [950-1110 pmol/L) (130-150 microU/mL)], while the blood glucose concentration was clamped at its basal value [4.9 +/- 0.1 (+/- SE) mmol/L in the normal subjects, 5.7 +/- 0.5 in the insulin-treated diabetic patients, and 5.5 +/- 0.3 in the untreated diabetic patients] by a variable glucose infusion. During the control period, arterial FFA concentrations were similar in the three groups, and they decreased to a comparable extent (less than 0.1 mmol/L) in response to insulin infusion. During the control period, the mean forearm FFA uptake was 2.5 +/- 0.5 mumol/L.min in the normal subjects, 2.9 +/- 0.5 in the insulin-treated patients, and 2.1 +/- 0.5 in the untreated diabetic patients. During the insulin infusion, FFA uptake was profoundly suppressed to similar levels in the normal subjects (0.9 +/- 0.1 mumol/L.min), the insulin-treated diabetic patients (1.1 +/- 0.3), and the untreated diabetic patients (0.9 +/- 0.1; P less than 0.001). Forearm glucose uptake was similar in the three groups during the control period. It increased during the insulin infusion, but the response in both diabetic groups was less than that in the normal subjects. The total amounts of glucose taken up by the forearm during the study period were 5.2 +/- 0.7, 2.6 +/- 0.5, and 2.1 +/- 0.6 mmol/L.min in the normal subjects, the insulin-treated diabetic patients, and the untreated diabetic patients, respectively (P less than 0.01). We conclude that 1) insulin-mediated glucose uptake by forearm skeletal muscle is markedly impaired in type II diabetes and improves only marginally after 2 weeks of intensive insulin therapy; 2) in contrast, no appreciable abnormality in forearm FFA metabolism is demonstrable in insulin-treated type II diabetic patients; and 3) FFA do not contribute to the insulin-treated skeletal muscle insulin resistance that occurs in patients with type II diabetes mellitus.

Adult↗
PubMed1994

Role of insulin and free fatty acid (FFA) availability on regional FFA kinetics in the human forearm.

To determine the role of insulin and free fatty acid (FFA) concentration in the regulation of FFA metabolism, forearm FFA fluxes were quantified in 16 healthy volunteers by combining the forearm perfusion technique with the infusion of [3H]palmitate. Three groups of studies were performed. In study 1 (n = 6), a systemic insulin infusion (1.2 mU/kg.min) was performed for 120 min while euglycemia was maintained by a variable glucose infusion. In Study 2 (n = 5), insulin (0.05 mU/kg.min) was infused into the brachial artery to expose the forearm tissues to the same insulin level as in study 1. In study 3 (n = 5), heparin was infused to raise plasma FFA concentration to 1-1.5 mmol/L. At 60 min, an intrabrachial insulin infusion was added as in study 2 and maintained for 60 min. During systemic insulin infusion, plasma FFA concentration fell to 0.09 +/- 0.02 mmol/L. Forearm FFA uptake (FFA-U) decreased from the basal value of 2.54 +/- 0.52 to 0.95 +/- 0.10 mumol/L.min (P < 0.05). Likewise, forearm FFA release (FFA-R) fell to 1.0 +/- 0.31 mumol/L.min (P < 0.05). With local insulin administration, both FFA levels and FFA-U remained unchanged, whereas FFA-R was markedly inhibited (from 1.78 +/- 0.23 to 1.04 +/- 0.24 mumol/L.min; P < 0.05). In study 3 (heparin infusion), FFA levels rose to 1.17 +/- 0.12 mmol/L due to a 4-fold increase in FFA-R (from 1.18 +/- 0.36 to 6.92 +/- 2.40 mumol/L.min; P < 0.05). FFA-U rose from the basal value of 2.50 +/- 0.82 to 6.92 +/- 1.95 mumol/L.min (P < 0.05). Addition of intrabrachial insulin did not modify FFA-U, whereas heparin activation of FFA-R was only partially antagonized (4.53 +/- 2.40 mumol/L.min; 0.01 < P < 0.05 vs. heparin alone). The data demonstrate that plasma FFA concentration is the main determinant of forearm FFA transport. Insulin exerts a direct inhibitory effect on FFA release and affects tissue FFA transport only indirectly through the fall in circulating FFA.

Adult↗
PubMed1997

Lack of relationship between vitamin D receptor genotype and forearm bone gain in healthy children, adolescents, and young adults.

Recent studies have suggested that genetic effects on bone mineral density (BMD) are related to allelic variation in the vitamin D receptor (VDR) gene. We examined 1) allelic influences of the VDR gene on BMD of the forearm, spine, hip, and whole body; and 2) allelic influences of the VDR gene on forearm BMD gain. Two hundred and seventy-three healthy boys and girls, aged 8.2-16.5 yr, at baseline were eligible. Forearm BMD was assessed with single photon absorptiometry at baseline. BMD gain was calculated as the annual percent change in BMD measured by single photon absorptiometry from the baseline and after 3.8 +/- 0.1 (+/-SD) yr. Calcium intake and physical activity were assessed by a detailed questionnaire at baseline and after 1 yr. VDR alleles were determined by BsaMI endonuclease restriction fragment analysis after PCR amplification. No significant differences in forearm BMD gain or in BMD assessed at the forearm, spine, hip, and whole body were observed among the three VDR genotypes. These findings did not change after adjusting for environmental factors such as calcium intake and physical activity or age, weight, height, and changes in weight and height during the observation period. In conclusion, our data do not support the idea that VDR genotypes are related to BMD gain or to BMD at the forearm, hip, spine, and whole body in healthy boys and girls, aged 8-21 yr. VDR genotyping is probably of little use for the detection of individuals who would benefit from increased calcium and physical activity to increase their peak bone densities.

Absorptiometry, Photon↗
PubMed2003

Forearm hyperemia is a better marker than carotid intima-media thickness or ankle-brachial index for coronary artery disease in Japanese males under 65.

Forearm hyperemia, carotid intima-media thickness (IMT), and ankle-brachial pressure index (ABI) are subclinical markers associated with coronary artery disease (CAD). However, it is not known which marker is most highly correlated with CAD. We therefore compared these three parameters in the same patients under 65 years of age. In 40 males with documented CAD (mean age, 53 years), we measured forearm hyperemia by plethysmography, carotid IMT by B-mode ultrasound, and ABI by Doppler ultrasonography. Microalbuminuria, serum lipids, glucose and C-reactive protein (CRP) were also measured. Thirteen normal males served as controls (mean age, 49 years). Compared with normal subjects, CAD patients had lower hyperemia (42 vs. 92%; p < 0.001) and greater carotid IMT (0.81 vs. 0.67 mm; p < 0.01), but ABI was similar. The sensitivity of forearm hyperemia (72%) was higher than that of carotid IMT (22%) or ABI (3%) (abnormal criteria: forearm hyperemia < 60%, carotid IMT 21.0 mm, and ABI < 0.9). The patients had higher serum low-density lipoprotein (LDL) cholesterol, glucose and CRP, and lower high-density lipoprotein (HDL) cholesterol than the controls. Albuminuria was present in 49% of patients. Subclinical markers were further analyzed by age (35-54 vs. 55-64 years). The sensitivity of carotid IMT was lower in the younger patients (4% vs. 33%), while that of forearm hyperemia (69% vs. 75%) and albuminuria (47% vs. 52%) did not change with age. While carotid ultrasound was useful in older patients ( > or = 55 years), forearm hyperemia and microalbuminuria were sensitive markers irrespective of age. ABI was not useful in the Japanese men with CAD under age 65.

Adult↗