Perinatal intermittent hypoxia increases early susceptibility to ANG II-induced hypertension in adult male but not in female Sprague–Dawley rats

Abstract

Prenatal, perinatal, and adulthood exposure to chronic intermittent hypoxia (IH) increases blood pressure in rodents. Males exposed to chronic IH have higher blood pressure vs females. However, it is unknown if this same sex difference exists with acute perinatal IH. We tested the hypothesis that acute perinatal IH increases baseline blood pressure and enhances sensitivity to angiotensin II-induced hypertension in male Sprague Dawley rats. Male and female pups were randomized to control (room air) or IH (10 minutes of ~10% O2 three times/day) for the first 8 days of life. IH decreased oxygen saturation, confirmed via pulse oximeter. Pups were weaned at postnatal day 21. Blood pressure was measured via telemetry beginning at 14 weeks of age and analyzed separated into light and dark phase to assess circadian rhythm. Osmotic mini-pumps to deliver angiotensin II were implanted at 15 weeks of age. Perinatal IH exposure did not alter baseline blood pressure. One week of Ang II treatment increased blood pressure in the light and dark periods in males exposed to IH vs control; there was no effect in females. Blood pressure among groups was comparable following 2 weeks of angiotensin II infusion. Perinatal IH did not change circadian rhythm. Following angiotensin II treatment, indices of renal injury were measured. Perinatal IH did not alter kidney size, structure, nephron number or creatinine clearance. These data indicate that acute perinatal IH enhances early angiotensin II-induced hypertension in males, independent of nephron loss or decreases in body weight or kidney function.