In patients with the metabolic syndrome (MetS), the facilitatory effect of insulin on forearm vasodilator responsiveness to different stimuli is impaired. Whether the RhoA/Rho kinase (ROCK) pathway is involved in this abnormality is unknown. We tested the hypotheses that, in MetS patients, ROCK inhibition with fasudil restores insulin-stimulated vasodilator reactivity and that oxidative stress plays a role in this mechanism. Endothelium-dependent and -independent forearm blood flow responses to acetylcholine (ACh) and sodium nitroprusside (SNP), respectively, were assessed in MetS patients (n=8) and healthy controls (n=5) before and after the addition of fasudil (200 µg/min) to an intra-arterial infusion of insulin (0.1 mU/kg/min). In MetS patients (n=5), fasudil was also infused without hyperinsulinemia. The possible involvement of oxidative stress in the effect of fasudil during hyperinsulinemia was investigated in MetS patients (n=5) by infusing vitamin C (25 mg/min). In MetS patients, compared to saline, fasudil enhanced endothelium-dependent and -independent vasodilator responses during insulin infusion (p<0.001 and p=0.008, respectively), but not in the absence of hyperinsulinemia (p=0.25 and p=0.13, respectively). By contrast, fasudil did not affect vasoreactivity to ACh and SNP during hyperinsulinemia in controls (p=0.11 and p=0.56, respectively). In MetS patients, fasudil added to insulin and vitamin C did not further enhance vasodilation to ACh and SNP (p= 0.15 and p=0.43, respectively). In the forearm circulation of patients with the MetS, ROCK inhibition by fasudil improves endothelium-dependent and -independent vasodilator responsiveness during hyperinsulinemia; increased oxidative stress seems to be involved in the pathophysiology of this phenomenon.

Schinzari, F., Mores, N., Cardillo, C., Rho Kinase Inhibition Improves Forearm VasodilatorResponsiveness During Hyperinsulinemia in the Metabolic Syndrome., <<AMERICAN JOURNAL OF PHYSIOLOGY: ENDOCRINOLOGY AND METABOLISM>>, 2012; 2012 (N/A): 1-5. [doi:22829585] [http://hdl.handle.net/10807/28773]

Rho Kinase Inhibition Improves Forearm Vasodilator Responsiveness During Hyperinsulinemia in the Metabolic Syndrome.

Schinzari, Francesca;Mores, Nadia;Cardillo, Carmine
2012

Abstract

In patients with the metabolic syndrome (MetS), the facilitatory effect of insulin on forearm vasodilator responsiveness to different stimuli is impaired. Whether the RhoA/Rho kinase (ROCK) pathway is involved in this abnormality is unknown. We tested the hypotheses that, in MetS patients, ROCK inhibition with fasudil restores insulin-stimulated vasodilator reactivity and that oxidative stress plays a role in this mechanism. Endothelium-dependent and -independent forearm blood flow responses to acetylcholine (ACh) and sodium nitroprusside (SNP), respectively, were assessed in MetS patients (n=8) and healthy controls (n=5) before and after the addition of fasudil (200 µg/min) to an intra-arterial infusion of insulin (0.1 mU/kg/min). In MetS patients (n=5), fasudil was also infused without hyperinsulinemia. The possible involvement of oxidative stress in the effect of fasudil during hyperinsulinemia was investigated in MetS patients (n=5) by infusing vitamin C (25 mg/min). In MetS patients, compared to saline, fasudil enhanced endothelium-dependent and -independent vasodilator responses during insulin infusion (p<0.001 and p=0.008, respectively), but not in the absence of hyperinsulinemia (p=0.25 and p=0.13, respectively). By contrast, fasudil did not affect vasoreactivity to ACh and SNP during hyperinsulinemia in controls (p=0.11 and p=0.56, respectively). In MetS patients, fasudil added to insulin and vitamin C did not further enhance vasodilation to ACh and SNP (p= 0.15 and p=0.43, respectively). In the forearm circulation of patients with the MetS, ROCK inhibition by fasudil improves endothelium-dependent and -independent vasodilator responsiveness during hyperinsulinemia; increased oxidative stress seems to be involved in the pathophysiology of this phenomenon.
Inglese
http://ajpendo.physiology.org/content/early/2012/07/19/ajpendo.00206.2012.reprint
Schinzari, F., Mores, N., Cardillo, C., Rho Kinase Inhibition Improves Forearm VasodilatorResponsiveness During Hyperinsulinemia in the Metabolic Syndrome., <>, 2012; 2012 (N/A): 1-5. [doi:22829585] [http://hdl.handle.net/10807/28773]
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/10807/28773
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