Elevated body fat in rats by the dietary nitric oxide synthase inhibitor, L-N omega nitroarginine.

The influence of the dietary nitric oxide (NO) synthase inhibitor, L-N omega nitroarginine (L-NNA) on body fat was examined in rats. In experiment 1, all rats were fed with the same amount of diet with or without 0.02% L-NNA for 8 wk. L-NNA intake caused elevations in serum triglyceride and body fat, and reduction in serum nitrate (a metabolite of nitric oxide). The activity of hepatic carnitine palmitoyltransferase was reduced by L-NNA. In experiment 2, rats were fed for 8 wk with the same amount of diets with or without 0.02% L-NNA supplemented or not with 4% L-arginine. The elevation in body fat, and the reductions in serum nitrate and in the activity of hepatic carnitine palmitoyltransferase by L-NNA were all suppressed by supplemental L-arginine. The results suggest that lower NO generation elevated not only serum triglyceride, but also body fat by reduced fatty acid oxidation.

Developmental spectrum of cardiac outflow tract anomalies encompassing transposition of the great arteries and dextroposition of the aorta: pathogenic effect of extrinsic retinoic acid in the mouse embryo.

We previously reported that retinoic acid shows a dose-dependent differential induction of various cardiac outflow anomalies: transposition of the great arteries is induced mainly by a high dose (70 mg/kg) and dextroposition of the aorta by a low dose (40-60 mg/kg; Yasui et al., 1995). We subsequently delineated the aberrant outflow tract septation process leading to the transposition (Yasui et al., 1997). The aim of the present study was to illustrate a spectrum of developmental abnormalities by examining mouse embryos treated with a low dose of retinoic acid and comparing them with embryos administered a high dose. We employed in situ observation on live embryos to discern the blood flow streams and scanning electron microscopy to clarify the internal structure. The embryos treated with a low dose of retinoic acid showed several basic phenotypes common to the high dose retinoic acid group, although variable and relatively mild, such as hypoplasia and dysplasia in the proximal outflow cushions, decreased counter-clockwise rotation in the distal outflow tract, and deviation of the edges of the developing outflow septum. In typical cases, the right-sided edge of the developing outflow septum shifted ventrally by various degrees, allowing for the right ventricle-to-aorta pathway, whereas the left-sided edge preserved the continuity with the interventricular septum, as in the normal embryo. These findings indicate that morphogenesis of dextroposition of the aorta and transposition of the great arteries are not only distinct but also show some basic pathways in common.