title: Chronic hypoxia, pregnancy, and endothelium-mediated relaxation in guinea pig uterine and thoracic arteries.
abstract: Vasodilation that occurs during normal pregnancy is associated with enhanced relaxation and decreased contractile response to agonists, which are in part due to increased stimulated and basal nitric oxide (NO). In preeclampsia and/or pregnancies carried at high altitude (HA), this normal vascular adjustment 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 sought to determine whether altitude interfered with effects of pregnancy on endothelium-dependent relaxation through a reduction in stimulated NO. We examined the relaxation response to ACh in UA and bradykinin in thoracic arteries (TA) and effects of NO inhibition with 200 microM N(G)-nitro-L-arginine (L-NNA) in arterial rings isolated from nonpregnant and pregnant guinea pigs 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 relaxation. The effect of L-NNA on the relaxation response to ACh was less in 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 data suggest that effects of NO inhibition are diminished in UA during pregnancy at HA. Additional studies are needed to confirm whether these effects are mediated through inhibition of stimulated NO. HA exposure did not inhibit relaxation to ACh, perhaps because of stimulation of other vasodilators.
authors.affiliation: Women's Health Research Center, University of Colorado Health Sciences Center, Denver 80262, USA. marguerite.white@uchsc.edu
authors.forename: M M
authors.initials: MM
authors.lastname: White
authors.forename: R E
authors.initials: RE
authors.lastname: McCullough
authors.forename: R
authors.initials: R
authors.lastname: Dyckes
authors.forename: A D
authors.initials: AD
authors.lastname: Robertson
authors.forename: L G
authors.initials: LG
authors.lastname: Moore
mesh_terms: D000531:Altitude; D000818:Animals; D002908:Chronic Disease; D004727:Endothelium / Q000502:physiology; D004730:Endothelium, Vascular / Q000502:physiology*; D005260:Female; D006168:Guinea Pigs; D000860:Hypoxia / Q000503:physiopathology*; D009126:Muscle Relaxation / Q000502:physiology; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000502:physiology*; D013895:Thoracic Arteries / Q000502:physiology / Q000503:physiopathology; D014599:Uterus / Q000502:physiology*; D014664:Vasodilation / Q000502:physiology