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Notes: 1. The aim of the present study was to determine whether anti-oxidant therapy with vitamin E and/or cholesterol-lowering therapy with simvastatin would augment resting forearm blood flow (FBF) and metabolic vasodilation in response to exercise and improve endothelial function in young patients with hypercholesterolaemia.2. Endothelium-dependent and -independent, nitric oxide (NO)-mediated vasodilation have been shown to be impaired in young, otherwise healthy subjects with hypercholesterolaemia. Recent experimental and clinical studies suggest that vascular function may be improved with anti-oxidant or cholesterol- lowering therapy, although these treatments may be synergistic.3. We compared FBF at rest, in response to isotonic exercise, the endothelium-dependent vasodilator acetylcholine (ACh), the endothelium-independent vasodilator sodium nitroprusside (SNP) and the NO synthase inhibitor NG-monomethyl-L-arginine (L-NMMA) in 26 young, otherwise healthy volunteers (mean (±SD) age 29±7 years; 14 female, 12 male) with hypercholesterolaemia, before and after 6 months treatment with vitamin E, simvastatin and/or placebo. Treatment was randomized, double-blinded in a 2 × 2 factorial design. Forearm blood flow was measured using venous occlusion plethysmography.4. Vitamin E therapy increased plasma α-tocopherol from 39.5±9.6 to 75.7±33.8 μmol/L (P 〈 0.001). Simvastatin reduced total cholesterol from 6.9±1.7 to 4.9±0.8 mmol/L and low- density lipoprotein (LDL) from 4.8±1.7 to 3.0±0.7 mmol/L (both P 〈 0.001), although total and LDL–cholesterol also decreased slightly in the placebo group. Vitamin E increased resting FBF from 2.1±0.3 to 2.4±0.3 mL/100 mL per min (P = 0.04) and decreased resting forearm vascular resistance from 42.1±4.2 to 36.1±3.4 units (P = 0.01), but the reduction in resting FBF with L-NMMA was not affected. Vasodilation in response to isotonic exercise, ACh and SNP was similar before and after treatment in the placebo, vitamin E, simvastatin and in the combined vitamin E–simvastatin groups. NG-Monomethyl-L-arginine infusion reduced resting FBF and functional hyperaemia in response to exercise and these responses were not altered by treatment.5. These data suggest that while vitamin E therapy augments resting FBF and reduces forearm vascular resistance in young hypercholesterolaemic subjects, these effects may not be via NO-dependent pathways. Metabolic vasodilation and responses to the NO-mediated vasodilators ACh and SNP were not favourably affected by anti-oxidant or cholesterol-lowering therapy, either alone or in combination.

Notes: 1. The aim of the present study was to determine the effects of long-term oestrogen on resistance vessel reactivity in biological males.2. Recent studies have demonstrated that long-term oestrogen therapy favourably alters the lipid profile and improves vasodilator function in the conduit arteries of biological males. Whether a similar benefit is exerted on the resistance circulation is not known. Therefore, we examined the effects of long-term oestrogen therapy on skeletal muscle resistance vessel function in biological males and the potential mechanisms by which it may exert its effects.3. Forearm blood flow (FBF) and resistance were compared in 15 male-to-female transsexuals being prescribed oestrogen, with 14 age-matched healthy males, at rest and in response to the endothelium-dependent nitric oxide (NO) vasodilator acetylcholine (ACh), the endothelium-independent but NO-mediated vasodilator sodium nitroprusside (SNP), the endothelium- independent and non-NO-mediated vasodilator verapamil (VER) and the endothelium-independent vasoconstrictor phenylephrine (PE).4. Basal blood flows were similar in the two groups. However, the male-to-female transsexuals had a significant upward and leftward shift in FBF responses to ACh compared with males, with a 52% increase in FBF responses at the highest dose of ACh used. Forearm blood flow in transsexuals rose from a mean (±SEM) baseline level of 3.02±0.25 to a maximum of 19.5± 2.59 mL/min per 100 mL forearm tissue (compared with 3.24±0.41 and 9.43±1.97 mL/min per 100 mL forearm tissue, respectively, in males) with the highest dose of ACh (+2.73 μg/min per 100 mL; P 〈 0.0005). Forearm vascular resistance was also significantly reduced in transsexuals compared with males (P 〈 0.05). Vasodilator responses to SNP, VER and PE were similar in both groups.5. There were no differences observed in total cholesterol and low-density lipoprotein–cholesterol levels. However, male- to-female transsexuals had 20% higher high-density lipo-protein–cholesterol levels compared with males (1.57±0.11 vs 1.26±0.08 mmol/L, respectively; P 〈 0.05) and 47% higher triglyceride levels (P 〈 0.005). Serum testosterone levels (an index of oestrogen therapy) was a predictor of responses to endothelium-dependent vasodilation (rs = –0.50; P 〈 0.01).6. Long-term oestrogen therapy enhances endothelium-dependent vasodilation in the skeletal muscle microcirculation of biological males. The effects appear to be selective because endothelium-independent vasodilation and vasoconstriction are not altered.