Background-Impaired nitric oxide (NO) activity is an early event in the pathogenesis of cardiovascular disease, resulting from either reduced NO formation or increased NO degradation. Administration of tetrahydrobiopterin (BH 4 ), an essential cofactor for NO production, could restore NO activity in familial hypercholesterolemia (FH). Because folates have been suggested to stimulate endogenous BH 4 regeneration, we hypothesized that administration of 5-methyltetrahydrofolate (5-MTHF, the active circulating form of folate) might improve NO formation in FH. Methods and Results-We studied the effects of 5-MTHF on NO bioavailability in vivo in 10 patients with FH and 10 matched control subjects by venous occlusion plethysmography, using serotonin and nitroprusside as endotheliumdependent and -independent vasodilators. In vitro, we investigated the effect of 5-MTHF on NO production by recombinant endothelial NO synthase (eNOS) by use of [ 3 H]arginine to [ 3 H]citrulline conversion. We also studied the effects of 5-MTHF on superoxide generation by eNOS and xanthine oxidase (XO) by use of lucigenin chemiluminescence. The impaired endothelium-dependent vasodilation in FH (63% versus 90% in control subjects) could be reversed by coinfusion of 5-MTHF (117% vasodilation), whereas 5-MTHF had no significant effect on endothelium-dependent vasodilation in control subjects. 5-MTHF did not influence basal forearm vasomotion or endothelium-independent vasodilation. 5-MTHF had no direct effect on in vitro NO production by eNOS. However, we did observe a dose-dependent reduction in both eNOS-and XO-induced superoxide generation. Conclusions-These results show that the active form of folic acid restores in vivo endothelial function in FH. It is suggested from our in vitro experiments that this effect is due to reduced catabolism of NO. (Circulation. 1998;97:237-241.)

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Our data show that nifedipine improves endothelial function in hypercholesterolemia. It is suggested from our in vitro experiments that this effect is due to reduced NO degradation.

Large-basis CI calculations are performed on the van der Waals complexes Ar-HC1 and (H,O),. It is shown that a reasonable estimate of the CI basis-set superposition error is obtained from a ghost calculation involving the orbitals of the monomer and only the virtual orbitals of the ghost.Both basis-set superposition error corrections and size-consistency corrections are of vital importance to obtain a reliable potential-energy surface.For Ar-HC1 the minima of the potential are predicted within 50 phartree of the experimental surface, viz. -804 phartree for the Ar-HCl orientation and -565 phartree for the HC1-Ar geometry.The water dimer van der Waals minimum is estimated to be -4.9 kcal mol-l, which is less deep then the experimentally derived minimum of -5.4 kcal mol-l, but just within the experimental error limit.

New anisotropic potential energy surfaces of the Hartree-Fock plus damped dispersion (HFD) type have been obtained for the N2-Ne and N2-Ar interactions. The SCF energies utilized in constructing the short-range part of the interactions were computed at 20 points on each surface by using basis sets of double zeta plus polarization quality. Anisotropic C 6 and Cs dispersion coefficients, utilized in constructing the long-range part of the interaction, have been calculated with a recently obtained combining rule. Several procedures are introduced for estimating the anisotropic damping factors used in the description of the correlation energy contributions in the HFD model. The essential differences amongst the surfaces reported here arise from these estimates. Comparisons are made with other available anisotropic N2-Ne and N2-Ar surfaces. The predictive ability of all surfaces with respect to the temperature dependence of the interaction second virial coefficient, BI2(T ), has also been tested. For the N2-Ne system only the present HFD3 surface gives good agreement with the experimental interaction second virial coefficients over a wide temperature range. Similarly, for the Nz-Ar system the surface of Candori et al. [1983, Chem. Phys. Lett., 102, 412], which was partially determined using the second virial coefficient data, and the present HFD1 surface give good agreement with experimental virial data.