F. Vittone

Effects of glucose tolerance on the changes provoked by glucose ingestion in microvascular function

Aims/hypothesisHyperglycaemia and hyperinsulinaemia have opposite effects on endothelium-dependent vasodilatation in microcirculation, but the net effect elicited by glucose ingestion and the separate influence of glucose tolerance are unknown.MethodsIn participants with normal glucose tolerance (NGT), impaired glucose tolerance (IGT) or diabetic glucose tolerance, multiple plasma markers of both oxidative stress and endothelial activation, and forearm vascular responses (plethysmography) to intra-arterial acetylcholine (ACh) and sodium nitroprusside (SNP) infusions were measured before and after glucose ingestion. In another IGT group, we evaluated the time-course of the skin vascular responses (laser Doppler) to ACh and SNP (by iontophoresis) 1, 2 and 3xa0h into the OGTT; the plasma glucose profile was then reproduced by means of a variable intravenous glucose infusion and the vascular measurements repeated.ResultsFollowing oral glucose, plasma antioxidants were reduced by 5% to 10% (pu2009<u20090.01) in all patient groups. The response to acetylcholine was not affected by glucose ingestion in any group, while the response to SNP was attenuated, particularly in the IGT group. The ACh:SNP ratio was slightly improved therefore in all groups, even in diabetic participants, in whom it was impaired basally. A time-dependent improvement in ACh:SNP ratio was also observed in skin microcirculation following oral glucose; this improvement was blunted when matched hyperglycaemia was coupled with lower hyperinsulinaemia (intravenous glucose).Conclusions/interpretationRegardless of glucose tolerance, oral glucose does not impair endothelium-dependent vasodilatation either in resistance arteries or in the microcirculation, despite causing increased oxidative stress; the endogenous insulin response is probably responsible for countering any inhibitory effect on vascular function.

Endothelium-dependent vasodilation at peripheral microvascular level in hypertensive patients before and after therapy with nebivolol

Background: Nebivolol is a new beta-adrenergic blocking agent which has been shown to cause vasodilation when infused in the forearm vascular bed both in normotensive and in hypertensive subjects, and this effect is probably mediated by the activation of the L-arginine/NO pathway. Aim of the study: to investigate cutaneous microvascular function in hypertensive (HT) patients before and after treatment with Nebivolol. Methods: in 11 never treated essential mild to moderate HT patients (mean age 48 69 years, 8 males, mean SBP/DBP 150 68/10064 mmHg) and in 20 normotensive controls (NT, mean age 50 67 years, mean SBP/DBP 118612/7269 mmHg), skin blood flow (SBF) was studied by means of laser doppler flowmetry (LDF) at baseline and after administration by iontophoresis of stepwise doses of Acetylcholine (ACh) and Sodium Nitroprusside (SNP), in order to explore the endothelium-dependent and independent vasodilation. In the HT group, the same protocol was repeated after 15 to 21 days of treatment with Nebivolol (5mg/die). Results: SBF significantly increased with ACh and SNP in NT and HT(p,.05 vs basal). During Nebivolol, blood pressure significantly decreased in all patients (mean SBP/DBP 129 612/8169 mmHg, p,.05 vs baseline). SBF response to both vasoactive agents did not significantly differ after therapy in the overall population. However, when the doseresponse curves to ACh in HT patients were compared to those obtained in NL, we could point out two subgroups: A) with a similar to normal, or enhanced response to ACh (SBFmax-SBFbasal .SBFmean-1sd than NT), B) with a depressed response to ACh (SBFmaxSBFbasal #SBFmean-1sd than NT). After therapy, group B showed significantly increased vasodilatory response to ACh, while group A showed a decreased one, as compared to pre-treatment response (ANOVA, p.,.05 vs pre-treatment). No differences were present when comparing SNP dose-response curves before and after Nebivolol. Conclusion: in patients with arterial hypertension, Nebivolol selectively improves endothelium-dependent microcirculatory vasodilation in patients with basally blunted response. By contrast, patients with basally normal response to ACh show a reduction in microcirculatory response, probably related to prevalence of peripheral beta-blocking effect when pre-treatment endothelium dependent vasodilation is preserved.