Prenatal exposure to methamphetamine in rats induces endothelial dysfunction in male but not female adult offspring.

Abstract

In utero exposure to methamphetamine results in significant developmental, neurological, and behavioral deficits in offspring. However, very little is known about the cardiovascular effects of prenatal methamphetamine exposure in adult offspring. We hypothesized that prenatal methamphetamine exposure causes adverse cardiovascular effects in adult offspring. The aims of this study were to test the effects of prenatal methamphetamine exposure on blood pressure and endothelial function in male and female adult rat offspring. Pregnant rats were injected with methamphetamine (5mgkg-1day-1) or saline throughout pregnancy. Conscious blood pressure and vascular function in mesenteric-resistance arteries were measured in male and female adult offspring using tail cuff and myography, respectively (beginning at 8weeks old). In adult male offspring, but not in adult female offspring, endothelium-dependent relaxation to acetylcholine was impaired in methamphetamine-exposed compared to saline-exposed rats. Vascular relaxation to diethylamine NONOate diethylammonium salt was not impacted by gender or prenatal exposure. Prenatal methamphetamine exposure had no effect on systolic blood pressure in offspring of either gender. These data suggest that prenatal methamphetamine exposure adversely affects endothelial function in a sex-dependent manner. Clinically, these data suggest that adult males with a history of prenatal methamphetamine exposure may be at greater risk of developing cardiovascular disease due to endothelial dysfunction.