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.
|Numero di pagine||5|
|Rivista||AMERICAN JOURNAL OF PHYSIOLOGY: ENDOCRINOLOGY AND METABOLISM|
|Stato di pubblicazione||Pubblicato - 2012|
- RHO KINASE