Effects of pregnancy and chronic hypoxia on contractile responsiveness to alpha 1-adrenergic stimulation

Decreasedcontractile response to vasoconstrictors in uterine and nonuterinevessels contributes to increased blood flow to the uterine circulationduring normal pregnancy. Pregnancies complicated by preeclampsiaand/or chronic hypoxia show a reversal or diminution of thesepregnancy-associated changes. We sought to determine whether chronichypoxia opposes the reduction in contractile response in uterine andnonuterine vessels during normal pregnancy and, if so, whetherdecreased basal nitric oxide (NO) activity was involved. We examinedthe contractile response to phenylephrine (PE) in guinea pig uterineartery (UA), mesenteric artery (MA), and thoracic aorta (TA) ringsisolated from nonpregnant or pregnant guinea pigs that had been exposedthroughout gestation to either low (1,600 m,n = 47) or high (3,962 m,n = 43) altitude. In the UA, pregnancyreduced contractile sensitivity to PE and did so similarly at low andhigh altitude (EC₅₀: 4.0 × 10⁸ nonpregnant, 9.3 × 10⁸ pregnant at lowaltitude; 4.8 × 10⁸nonpregnant, 1.0 ×10⁸pregnant at high altitude; both P < 0.05). Addition of the NO synthase inhibitornitro-L-arginine (NLA; 200 mM)to the vessel bath increased contractile sensitivity in the pregnant UA(P < 0.05) and eliminated the effectof pregnancy at both altitutes. NLA also raised contractile sensitivityin the nonpregnant high-altitude UA, but contractile response withoutNLA did not differ in the high- and low-altitude animals. In the MA,pregnancy decreased contractile sensitivity to PE at high altitudeonly, and this shift was reversed by NO inhibition. In the TA, neitherpregnancy nor altitude affected contractile response, but NO inhibition raised contractile response in nonpregnant and pregnant TA at bothaltitudes. We concluded that pregnancy diminished contractile responseto PE in the UA, likely as a result of increased NO activity, and thatthese changes were similar at low and high altitude. Counter to ourhypothesis, chronic hypoxia did not diminish the pregnancy-associatedreduction in contractile sensitivity to PE or inhibit basal NO activityin the UA; rather it enhanced, not diminished, basal NO activity in thenonpregnant UA and the pregnant MA.