Insulin Stimulates Both Endothelin and Nitric Oxide Activity in the Human Forearm

Cardillo, Carmine; Nambi, Sridhar S.; Kilcoyne, Crescence M.; Choucair, Wassim; Katz, Arie; Quon, Michael J.; Panza, Julio A.

doi:10.1161/01.cir.100.8.820

Cited by 274 publications

(204 citation statements)

References 32 publications

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“…This pathophysiological link may be partly mediated by insulin resistance. [34][35][36][37] In this study, as the association between visceral adiposity and hypertension was independent of insulin resistance, visceral adiposity may affect hypertension through mechanisms unrelated to fasting plasma insulin.…”

Section: Discussionmentioning

confidence: 73%

Visceral adiposity, not abdominal subcutaneous fat area, is associated with high blood pressure in Japanese men: the Ohtori study

et al. 2011

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Visceral adiposity is considered to have a key role in cardiometabolic diseases. The purpose of this study is to investigate cross-sectionally the association between intra-abdominal fat area (IAFA) measured by computed tomography (CT) and high blood pressure independent of abdominal subcutaneous fat area (ASFA) and insulin resistance. Study participants included 624 Japanese men not taking oral hypoglycemic medications or insulin. Abdominal, thoracic and thigh fat areas were measured by CT. Total fat area (TFA) was calculated as the sum of abdominal, thoracic and thigh fat area. Total subcutaneous fat area (TSFA) was defined as TFA minus IAFA. Hypertension and high normal blood pressure were defined using the 1999 criteria of the World Health Organization. Multiple-adjusted odds ratios of hypertension for tertiles of IAFA were 2.64 (95% confidence interval, 1.35-5.16) for tertile 2, and 5.08 (2.48-10.39) for tertile 3, compared with tertile 1 after adjusting for age, fasting immunoreactive insulin, diabetes status, ASFA, alcohol consumption, regular physical exercise and smoking habit. IAFA remained significantly associated with hypertension even after adjustment for ASFA, TSFA, TFA, body mass index or waist circumference, and no other measure of regional or total adiposity was associated with the odds of hypertension in models, which included IAFA. Similar results were obtained for the association between IAFA and the prevalence of high normal blood pressure or hypertension. In conclusion, greater visceral adiposity was associated with a higher odds of high blood pressure in Japanese men.

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Section: Discussionmentioning

confidence: 73%

Visceral adiposity, not abdominal subcutaneous fat area, is associated with high blood pressure in Japanese men: the Ohtori study

et al. 2011

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“…ACh and insulin both act via the endothelium. Insulin's actions on vascular tone occur via effects on the balance between nitric oxide and endothelin production (9,31). Iontophoretically applied ACh is generally agreed to induce an endothelium-dependent vasodilation, but the relative contribution of the different mediators is still a matter of debate.…”

Section: Discussionmentioning

confidence: 99%

Insulin's microvascular vasodilatory effects are inversely related to peripheral vascular resistance in overweight, but insulin‐sensitive subjects

Hornstra

Serné

Eringa

et al. 2013

Obesity

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Objective: The mechanisms underlying obesity-related hypertension are incompletely understood. Microvascular dysfunction might play a role by increasing peripheral vascular resistance (PVR). Metabolic and microvascular effects of insulin are impaired in obesity, but how these impairments contribute to disturbed blood pressure homeostasis is unclear. Specifically, it is unknown whether local microvascular vasoactive effects of insulin play a role in determining systemic vascular resistance. The aim of this study was to investigate the association between PVR and local microvascular effects of insulin. Design and Methods: Thirty-seven healthy, overweight subjects (age 25-55 years, BMI 25-30 kg/m 2 ) were cross-sectionally studied. Local insulin-mediated vasodilation was measured using skin laser Doppler fluxmetry combined with transcutaneous iontophoresis of insulin. For comparison, local vasodilatory effects of acetylcholine and sodium nitroprusside were measured. PVR was calculated from mean arterial pressure and cardiac output, assessed by pulse-dye densitometry. Results: PVR was inversely correlated with insulin-mediated vasodilation (r ¼ À0.50; P < 0.01). This finding was maintained after adjustment for age, sex, blood pressure, and smoking. PVR was not associated with local microvascular effects of acetylcholine. Conclusions: Our study in overweight subjects suggests that insulin's role in the microvasculature may contribute to blood pressure control.

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“…The accumulation of metabolic vasodilators, myogenic and/or neurogenic mechanisms may play a role [18]. It seems unlikely that hyperinsulinaemia decreases sensitivity to vasoconstrictive effects, because, both in the isolated rat arteriole and in the human forearm, hyperinsulinaemia has been shown to increase vasoconstrictive effects by inducing endothelin-1 activity [19,20]. In humans, moreover, insulin has been shown to stimulate vasodilatory effects by inducing endothelial nitric oxide (NO) production [21].…”

Section: Discussionmentioning

confidence: 99%

Physiological hyperinsulinaemia increases intramuscular microvascular reactive hyperaemia and vasomotion in healthy volunteers

et al. 2004

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Aims/hypothesis. Insulin possesses vasodilatory actions that may be important in regulating its access to insulin-sensitive tissues. Our study aims to directly measure changes in response to insulin in the human skeletal muscle microcirculation. Measurement was by an implanted laser Doppler probe. Methods. We investigated changes in intramuscular and skin microvascular perfusion in 12 healthy individuals during a hyperinsulinaemic and a control clamp. We determined leg blood flow with plethysmography, finger skin functional capillary recruitment with capillaroscopy, endothelium-(in)dependent vasodilation by iontophoresis of acetylcholine and sodium nitroprusside, and leg intramuscular reactive hyperaemia and vasomotion with laser Doppler measurements. Results. Compared to the control study, hyperinsulinaemia (416±82 pmol/l) caused: (i) an increase in leg blood flow (1.0±1.0 vs 0.1±0.6 ml·min −1 ·100 ml, p<0.05); (ii) an increase in finger skin capillary recruitment (14.9±10.1 vs -5.6±11.0%, p<0.01); (iii) no change in baseline laser Doppler perfusion either in finger skin or leg muscle; (iv) a tendency to increase acetylcholine-mediated vasodilation (475±534 vs 114±337%, p=0.07) with no change in sodiumnitroprusside-mediated vasodilation (p=0.2) in finger skin; (v) an increase in intramuscular reactive hyperaemia (423±507 vs 0±220%, p<0.01); and (vi) a decrease in time needed to reach peak intramuscular perfusion (−3.6±3.0 vs 1.1±3.1 s, p<0.01). In addition, hyperinsulinaemia induced an increase in intramuscular vasomotion by increasing the contribution of frequencies between 0.01 and 0.04 Hz (p<0.05 for all), which probably represents increased endothelial and neurogenic activity. Conclusions/interpretation. Physiological hyperinsulinaemia not only stimulates total blood flow and skin microvascular perfusion, but also augments human skeletal muscle microvascular recruitment and vasomotion as detected directly by laser Doppler measurements.

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Insulin Stimulates Both Endothelin and Nitric Oxide Activity in the Human Forearm

Cited by 274 publications

References 32 publications

Visceral adiposity, not abdominal subcutaneous fat area, is associated with high blood pressure in Japanese men: the Ohtori study

Visceral adiposity, not abdominal subcutaneous fat area, is associated with high blood pressure in Japanese men: the Ohtori study

Insulin's microvascular vasodilatory effects are inversely related to peripheral vascular resistance in overweight, but insulin‐sensitive subjects

Physiological hyperinsulinaemia increases intramuscular microvascular reactive hyperaemia and vasomotion in healthy volunteers

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