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Am J Physiol Heart Circ Physiol (April 15, 2005). doi:10.1152/ajpheart.00191.2005
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Submitted on February 25, 2005
Accepted on April 5, 2005

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

Denise G Hemmings1, Sarah J Williams2, and Sandra T Davidge1*

1 Perinatal Research Centre, Departments of Obstetrics & Gynecology and Physiology, University of Alberta, Edmonton, Alberta, Canada
2 Perinatal Research Centre, Departments of Obstetrics & Gynecology and Physiology, University of Alberta, Edmonton, Alberta, Canada; Physiology, Centre for the Early Origins of Adult Health, School of Molecular and Biomedical Science, University of Adelaide, Adelaide, South Australia, Australia

* To whom correspondence should be addressed. E-mail: sandra.davidge{at}ualberta.ca.

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 month (7mo) offspring from hypoxic (12% O2; Hoff) or nutrient restricted (40% of control; NRoff) rat dams will show greater myogenic responses than their 4 month (4mo) littermates or control offspring (Coff) through impaired modulation by vasodilators. Growth restriction occurred in male Hoff (P<0.01), male NRoff (P<0.01) and female NRoff (P<0.02), but not female Hoff. Myogenic responses in mesenteric arteries from males but not females were increased at 7 mo in Hoff (P<0.01) and NRoff (P<0.05) versus Coff. There was less modulation of myogenic responses after inhibition of nitric oxide synthase (NOS; P<0.05), prostaglandin H synthase (PGHS; P<0.005) or both enzymes (P<0.001) in arteries from 7mo male Hoff versus Coff. Thus, reduced vasodilator modulation may explain elevated myogenic responses in 7mo male Hoff. In contrast, there was increased modulation of myogenic responses in arteries from 7mo female Hoff versus Coff or NRoff after inhibition of both enzymes (P<0.05). Thus, increased vasodilator modulation may maintain myogenic responses in female Hoff 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 male offspring more profoundly affected.




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