Hyperglycemia in pregnant rats causes gender-related vascular dysfunction in adult offspring: role of cyclooxygenase-2

Abstract

Exposure to maternal hyperglycemia induces hypertension and vascular dysfunction in adult male offspring. Because female offspring from several fetal programming models are protected from the effects of fetal insult, in this study we analyzed possible differences relative to gender in blood pressure and vascular function in hyperglycemia-programmed offspring. Hyperglycemia was induced on gestation day 7 (streptozotocin, 50 mg.kg⁻¹). Blood pressure, acetylcholine and phenylephrine/noradrenaline responses were analyzed in aorta and mesenteric resistance arteries (MRA) of 3-, 6- and 12-month-old male and female offspring. TxA₂ release was analyzed by commercial kits and superoxide anion (O₂⁻) production by dihydroethidium-emitted fluorescence. Male but not female offspring of hyperglycaemic dams (O-DR) had increased blood pressure than controls (O-CR). Contraction to phenylephrine increased and relaxation to acetylcholine was decreased only in aorta from 12-month-old male O-DR than age-matched O-CR. Contractile and vasodilator responses were preserved in both aorta and MRA from female O-DR in all ages. Preincubation with tempol, superoxide dismutase, indomethacin, NS-398, furegrelate or SQ29548 decreased contraction to phenylephrine and potentiated relaxation to acetylcholine in 12-month-old male O-DR aorta. In this artery, TxA₂ release and O₂⁻ generation were greater in O-DR than O-CR. In conclusion, exposure to hyperglycemia in utero results in sex-specific and age-dependent hypertension. The fact that vascular function is preserved in female O-DR, may in part explain the absence of hypertension in this group. On the other hand, the peripheral artery dysfunction associated with increased COX-2-derived contracting prostanoids production could underlie the increased blood pressure in male O-DR.

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