Increased myogenic tone in 7-month-old adult male but not female offspring from rat dams exposed to hypoxia during pregnancy

1 Perinatal Research Centre, Departments of Obstetrics and Gynecology and Physiology, University of Alberta, Edmonton, Alberta, Canada; and 2 Physiology, Centre for the Early Origins of Adult Health, School of Molecular and Biomedical Science, University of Adelaide, Adelaide, South Australia, Australia Submitted 25 February 2005 ; accepted in final form 5 April 2005 Intrauterine growth restriction (IUGR) increases the risk of cardiovascular disease later in life. Vascular dysfunction occurs in adult offspring from animal models of IUGR including maternal undernutrition, but the influence of reduced fetal oxygen supply on adult vascular function is unclear. Myogenic responses, essential for vascular tone regulation, have not been evaluated in these offspring. We hypothesized that 7-mo-old offspring from hypoxic (12% O 2 ; H) or nutrient-restricted (40% of control; NR) rat dams would show greater myogenic responses than their 4-mo-old littermates or control (C) offspring through impaired modulation by vasodilators. Growth restriction occurred in male H ( P < 0.01), male NR ( P < 0.01), and female NR ( P < 0.02), but not female H, offspring. Myogenic responses in mesenteric arteries from males but not females were increased at 7 mo in H ( P < 0.01) and NR ( P < 0.05) vs. C offspring. There was less modulation of myogenic responses after inhibition of nitric oxide synthase ( P < 0.05), prostaglandin H synthase ( P < 0.005), or both enzymes ( P < 0.001) in arteries from 7-mo male H vs. C offspring. Thus reduced vasodilator modulation may explain elevated myogenic responses in 7-mo male H offspring. In contrast, there was increased modulation of myogenic responses in arteries from 7-mo female H vs. C or NR offspring after inhibition of both enzymes ( P < 0.05). Thus increased vasodilator modulation may maintain myogenic responses in female H offspring at control levels. In summary, vascular responses in adult offspring from adverse intrauterine environments are impaired in a gender-specific, age-dependent, and maternal insult-dependent manner, with males more profoundly affected. fetal programming; undernutrition; nitric oxide; vascular function; gender Address for reprint requests and other correspondence: S. T. Davidge, Perinatal Research Centre, 220 Heritage Medical Research Centre, Univ. of Alberta, Edmonton, AB, Canada T6G 2S2 (E-mail: sandra.davidge{at}ualberta.ca )