Skeletal muscle blood flow is not a determinant of insulin resistance in essential hypertension

Hunter, SJ; Harper, Ray; Cn, Ennis; Sheridan, B.; Atkinson, A. B.; Pm, Bell

doi:10.1097/00004872-199715010-00007

Cited by 14 publications

(4 citation statements)

References 27 publications

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“…2B). The action of insulin in these animals r e flects the situation observed on insulin administration to some (9,39-41) but not all (42) hypertensive humans, where no decrease in vascular resistance is observed.…”

Section: Discussionmentioning

confidence: 56%

Acute vasoconstriction-induced insulin resistance in rat muscle in vivo.

1999

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Insulin-mediated changes in blood flow are associated with altered blood flow distribution and increased capillary recruitment in skeletal muscle. Studies in perfused rat hindlimb have shown that muscle metabolism can be regulated by vasoactive agents that control blood flow distribution within the hindlimb. In the present study, the effects of a vasoconstrictive agent that has no direct effect on skeletal muscle metabolism but that alters perfusion distribution in rat hindlimb was investigated in vivo to determine its effects on insulin-mediated vascular action and glucose uptake. We measured the effects of alpha-methylserotonin (alpha-met5HT) on mean arterial blood pressure, heart rate, femoral blood flow, hindlimb vascular resistance, and glucose uptake in control and euglycemic insulin-clamped (10 mU x min(-1) x kg(-1)) anesthetized rats. Blood flow distribution within the hindlimb muscles was assessed by measuring the metabolism of 1-methylxanthine (1-MX), an exogenously added substrate for capillary xanthine oxidase. Alpha-met5HT (20 microg x min(-1) x kg(-1)) infusion alone increased mean arterial blood pressure by 25% and increased hindlimb vascular resistance but caused no change in femoral blood flow. These changes were associated with decreased hindlimb 1-MX metabolism indicating less capillary flow. Insulin infusion caused decreased hindlimb vascular resistance that was associated with increased femoral blood flow and 1-MX metabolism. Treatment with alpha-met5HT infusion commenced before insulin infusion prevented the increase in femoral blood flow and inhibited the stimulation of 1-MX metabolism. Alpha-met5HT infusion had no effect on hindlimb glucose uptake but markedly inhibited the insulin stimulation of glucose uptake (P < 0.05) and was associated with decreased glucose infusion rates to maintain euglycemia (P < 0.05). A significant correlation (P < 0.05) was observed between 1-MX metabolism and hindlimb glucose uptake but not between femoral blood flow and glucose uptake. The results indicate that in vivo, certain types of vasoconstriction in muscle such as elicited by 5HT2 agonists, which prevent normal insulin recruitment of capillary flow, cause impaired muscle glucose uptake. Moreover, if vasoconstriction of this kind results from stress-induced increase in sympathetic outflow, then this may provide a clue as to the link between hypertension and insulin resistance that is often observed in humans.

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Section: Discussionmentioning

confidence: 56%

Acute vasoconstriction-induced insulin resistance in rat muscle in vivo.

1999

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“…This may explain why defects in blood flow have not been observed in previous studies performed in patients with essential hypertension. [15][16][17][18][19][20][21] Consistent with this hypothesis, Baron et al 23 and Utriainen et al, 22 who used 8 to 35 times higher doses of insulin than those used to study patients with essential hypertension, did find correlations between mean arterial pressure and leg blood flow in normal subjects. Our finding of a defect in mean blood flow in patients with essential hypertension at an insulin concentration of 450 mU/L is in line with the latter observations and provides the first evidence of a defect in the vasodilatory effect of insulin in these patients.…”

Section: Insulin and Mean Muscle Blood Flow In Essential Hypertensionmentioning

confidence: 84%

“…[15][16][17][18][19][20][21] In normal subjects, however, inverse relations have been found in two studies between mean arterial blood pressure and insulin-stimulated blood flow. 22,23 In the latter studies, 22,23 the insulin concentra-tions were high enough to clearly (on the average by 80% to 117%) increase blood flow above basal values, whereas in the studies performed in hypertensive subjects, [15][16][17][18][19][20][21] infusion of insulin either did not increase blood flow significantly or the increase was modest (10% to 30%). We hypothesized that if defects in insulin-stimulated blood flow do indeed characterize patients with essential hypertension, the stimulus, that is, the dose of insulin or duration of the insulin infusion, must be high enough to clearly increase blood flow in normal subjects.…”

mentioning

confidence: 99%

Preserved Relative Dispersion but Blunted Stimulation of Mean Flow, Absolute Dispersion, and Blood Volume by Insulin in Skeletal Muscle of Patients With Essential Hypertension

Laine

Knuuti²,

Ruotsalainen³

et al. 1998

Circulation

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“…7 However, interpretation of results from studies in older volunteers and patient groups is less clear; for example, in type 2 diabetes and hypertension there are data that report blunting of insulin-mediated vasodilation that parallels changes in insulin sensitivity, 8,9 although contrasting data report no defect in the vascular action of insulin. 10,11 However, it is possible that these conflicting results are due to other factors such as age, obesity, and dyslipidemia, which have been shown to be important determinants of both insulin action and vascular endothelial function. [12][13][14] In the present study, we hypothesized that insulin-resistant subjects (patients with essential hypertension and type 2 diabetes) would display blunting of both insulinmediated vasodilation and basal endothelial NO production compared with subjects carefully controlled for potentially confounding factors such as age, body mass index (BMI), and lipid profile.…”

mentioning

confidence: 99%

Insulin Action Is Associated With Endothelial Function in Hypertension and Type 2 Diabetes

et al. 2000

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Abstract-A primary defect in the vascular action of insulin may be a key intermediate mechanism that links endothelial dysfunction with reduced insulin-mediated cellular glucose uptake in metabolic and cardiovascular disorders. The present study was designed to characterize more fully the relations between insulin action and endothelial function in male patients with essential hypertension (H, nϭ9) or type 2 diabetes (D, nϭ9) along with healthy control subjects (C) matched for age, body mass index, and lipid profile. They attended for measurement of whole-body insulin sensitivity (MCR) by the hyperinsulinemic clamp technique (day 1) and forearm vasoreactivity in response to intra-arterial infusions of insulin/glucose (day 2) and N G -monomethyl-L-arginine (L-NMMA) and norepinephrine (day 3) by bilateral venous-occlusion plethysmography. Results expressed as meanϮSE MCR (mL/kg per minute) were 7.22Ϯ0.99 (C), 6.32Ϯ0.78 (H), and 5.06Ϯ0.53 (D). Insulin/glucose-mediated vasodilation (IGMV) was 17.1Ϯ5.6% (C), 17.2Ϯ5.5% (H), and 12.3Ϯ6.4% (D). L-NMMA vasoconstriction (LNV) was 37.9Ϯ5.1% (C), 37.5Ϯ2.3% (H), and 33.6Ϯ2.8% (D). There were no significant differences among groups for these parameters. Pooled correlation analyses revealed associations between MCR and IGMV (rϭ0.46, PϽ0.05), MCR and LNV (rϭ0.44, PϽ0.05), and IGMV and LNV (rϭ0.52, PϽ0.01). This study supports functional coupling between insulin action (both metabolic and vascular) and basal endothelial nitric oxide production in humans. Key Words: insulin Ⅲ endothelium Ⅲ nitric oxide Ⅲ hyperinsulinism Ⅲ hypertension, essential Ⅲ diabetes mellitus A bnormally reduced insulin-stimulated glucose uptake (insulin resistance) and vascular endothelial dysfunction are both features of metabolic syndromes and cardiovascular disorders. However, it is unclear whether this association is causal or a reflection of a common underlying pathophysiological mechanism. In addition to its metabolic and mitogenic actions, insulin is a directly acting vasodilator, an action that is both endothelium dependent 1 and enhanced by D-glucose 2 and L-arginine 3 uptake. It is therefore tempting to speculate that the vascular effect of insulin may be a key intermediate mechanism that links endothelial function with insulinmediated cellular glucose uptake. Indeed, in previous studies involving young healthy volunteers, we have demonstrated associations between insulin sensitivity and both basal endothelial nitric oxide (NO) production 4 and insulin-mediated vasodilation. 5 Others have shown associations between endothelial function and insulin-mediated vasodilation 6 and, recently, between insulin action (both metabolic and vascular) and microvascular function. 7 However, interpretation of results from studies in older volunteers and patient groups is less clear; for example, in type 2 diabetes and hypertension there are data that report blunting of insulin-mediated vasodilation that parallels changes in insulin sensitivity, 8,9 although contrasting data report no defect in the vascular actio...

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Skeletal muscle blood flow is not a determinant of insulin resistance in essential hypertension

Abstract: Differences in whole-body glucose uptake in hypertensive and control subjects are not likely to be related to differences in insulin-induced stimulation of muscle blood flow.

Cited by 14 publications

References 27 publications

Acute vasoconstriction-induced insulin resistance in rat muscle in vivo.

Acute vasoconstriction-induced insulin resistance in rat muscle in vivo.

Preserved Relative Dispersion but Blunted Stimulation of Mean Flow, Absolute Dispersion, and Blood Volume by Insulin in Skeletal Muscle of Patients With Essential Hypertension

Insulin Action Is Associated With Endothelial Function in Hypertension and Type 2 Diabetes

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