Abstract 1: Male Sprague Dawley Rats Exposed To Perinatal Hypoxia Are More Susceptible To Angiotensin II-induced Hypertension In Adulthood Vs Females

Abstract

Preterm infants (born prior to 37 weeks (wks) gestation) are susceptible to hypoxia, which predisposes to hypertension in later life. Underdeveloped organs, including the kidney, prevent preterm infants from effectively regulating blood volume and O 2 delivery. Since rat nephrogenesis completes ~ postnatal day (PND) 8, we hypothesized that exposure to hypoxia before nephrogenesis is complete will promote hypertension in adulthood. Male and female Sprague Dawley pups were randomized to Ctrl (room air) or intermittent hypoxia (IH) at PND 1 (n=6/group). IH pups were exposed to ~10% O 2 three times a day, 10 minutes/session, from PND 1-8. O 2 saturation was measured at PND 6. Mean arterial pressure (MAP) was measured via telemetry from ~14 – 16 wks of age. To determine the MAP response to a cardiovascular challenge, osmotic minipumps containing angiotensin (Ang) II (400 ng/kg/min) were implanted at 15 wks of age. IH pups had lower O 2 saturation vs ctrl (P O2 <0.05). Light cycle (LC) and dark cycle (DC) MAP were similar in all groups at baseline. Following treatment, LC-MAP was higher in IH-M vs Ctrl-M, but similar among female groups (P Int . = 0.04). IH animals had higher DC-MAP vs ctrl (P O2 = 0.02). IH decreased blood oxygen, suggesting a global decrease in oxygen delivery to organs, similar to what is seen with hypoxia. Perinatal IH alone did not increase MAP. However, this exposure did increase MAP in response to Ang II. While both males and females exposed to perinatal hypoxia had higher Ang II-induced hypertension vs ctrls in the dark cycle, this effect was preserved only in males in the light cycle. This suggests males are more susceptible to blood pressure effects of perinatal IH.