Immediate direct peripheral vasoconstriction in response to hyperinsulinemia and metformin in the anesthetized pig.

Elevated levels of insulin have been reported to induce both an arterial vasodilation mediated by nitric oxide (NO), and vasoconstriction mediated by endothelin and reactive oxygen radicals. Metformin, used to control blood glucose levels in type 2 diabetes, has also been shown to cause NO-mediated dilation of conduit arteries. It is possible that these contradictory vascular effects are due to a non-direct action on arteries. Therefore, the direct effect of high levels of insulin and metformin infusion on resistance artery diameter was evaluated. Experiments were carried out on the anesthetized pig; blood flow and pressure were measured in the iliac artery. An adjustable snare was applied to the iliac above the pressure and flow measurement site to induce step decreases (3-4 occlusions at 5 min intervals were performed for each infusion) in blood flow, and hence iliac pressure, and the conductance (deltaflow / deltapressure) calculated. Saline, insulin (20 and 40 mUSP/l/min), and metformin (1 microg/ml/min) were infused separately downstream of the adjustable snare and their effect on arterial conductance assessed. Insulin at both infusion rates and metformin caused a significant reduction in peripheral vascular conductance. In conclusion, hyperinsulinemia and metformin infusion constrict resistance arterial vessels in vivo.

Hydrogen peroxide alters sternohyoid muscle function.

Upper airway (UA) dilator muscles are critical for the maintenance of airway patency. Injury or fatigue to this group of muscles, as observed in patients with obstructive sleep apnoea (OSA) and animal models of OSA, may leave the UA susceptible to collapse. Although the mechanisms underlying respiratory muscle dysfunction are not completely understood, there is strong evidence suggesting a link between increased production of reactive oxygen species and altered muscle function. The aim of this study was to examine the effects of H2O2 on rat sternohyoid muscle function in vitro. Sternohyoid contractile and endurance properties were examined at 35 °C under control or hypoxic conditions. Studies were conducted in the presence of varying concentrations of H2O2 (0, 0.01, 0.1 and 1 mM). Muscle function was also examined in the presence of antioxidants [desferoxamine (DFX), catalase] and the reducing agent dithiothreitol (DTT). H2O2 decreased muscle endurance in a concentration-dependent manner. This was partially reversed by catalase, DFX and DTT. Our results suggest that oxidants may contribute to UA respiratory muscle dysfunction with implications for the control of UA patency in vivo.

Responses of iliac conduit artery and hindlimb resistance vessels to luminal hyperfructosemia in the anaesthetized pig.

AIMS: High fructose levels are found in diabetes mellitus, associated with high corn syrup diets, and have been claimed to cause hypertension. As the direct effects on conduit and resistance arteries have not been previously reported, we measured these in vivo in the anaesthetized pig with instrumented iliac arteries. METHODS: Experiments were performed on the iliac artery preparation in the anaesthetized pig: blood flow, diameter and pressure were measured in the iliac. RESULTS: The change in diameter of an occluded iliac artery segment filled with hyperfructosemic (15 µm) blood was 89.5 ± 22.1 µm (mean ± SE), contrasted with 7.7 ± 13.06 µm control (P = 0.005, paired t-test, n = 6). There was no significant difference when compared with blood containing both hyperfructosemic blood and the nitric oxide synthesis inhibitor, N(G)-nitro-l-arginine methyl ester (250 µg mL(-1)). Step changes in pressure and flow were achieved by progressive arterial stenosis during control saline and 15 µm min(-1) fructose downstream intra-arterial infusions. Linear regression of the step changes in blood pressure versus the instantaneous step changes in blood flow showed a statistically significant decrease in slope of the conductance (P < 0.001, analysis of covariance), indicating an increase in instantaneous peripheral vascular resistance. Peripheral autoregulation and conduit artery shear-stress-mediated dilatation were not significantly altered. CONCLUSION: An elevated level of fructose caused dilatation of a conduit artery but constriction of resistance vessels. The latter effect could account, if maintained long-term, for the hypertension claimed to be due to hyperfuctosemia.