Chronic hypoxia, pregnancy, and endothelium-mediated relaxation in guinea pig uterine and thoracic arteries

Vasodilation that occurs during normal pregnancy is associated with enhance d relaxation and decreased contractile response to agonists, which are in p art due to increased stimulated and basal nitric oxide (NO). In preeclampsi a and/or pregnancies carried at high altitude (HA), this normal vascular ad justment is reversed or diminished. We previously reported that HA exposure did not inhibit the pregnancy-associated decrease in contractile response to agonist or basal NO in guinea pig uterine arteries (UA). We therefore so ught to determine whether altitude interfered with effects of pregnancy on endothelium-dependent relaxation through a reduction in stimulated NO. We e xamined the relaxation response to ACh in UA and bradykinin in thoracic art eries (TA) and effects of NO inhibition with 200 mu M N-G-nitro-L-arginine (L-NNA) in arterial rings isolated from nonpregnant and pregnant guinea pig s exposed throughout gestation to low altitude (LA, 1,600 m, n = 26) or HA (3,962 m, n = 22). In pregnant UA, relaxation to ACh was enhanced (P< 0.05) at both altitudes and NO inhibition diminished, but did not reverse, ACh r elaxation. The effect of L-NNA on the relaxation response to ACh was less i n HA than in LA animals (P = 0.0021). In nonpregnant UA, relaxation to ACh was similar in LA and HA animals. L-NNA reversed the relaxation response to ACh at HA but not at LA. In TA, relaxation to bradykinin was unaltered by pregnancy or altitude and was completely reversed by NO inhibition. These d ata suggest that effects of NO inhibition are diminished in UA during pregn ancy at HA. Additional studies are needed to confirm whether these effects are mediated through inhibition of stimulated NO. HA exposure did not inhib it relaxation to ACh, perhaps because of stimulation of other vasodilators.