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

Decreased contractile response to vasoconstrictors in uterine and nonuterin e vessels contributes to increased blood flow to the uterine circulation du ring normal pregnancy. Pregnancies complicated by preeclampsia and/or chron ic hypoxia show a reversal or diminution of these pregnancy-associated chan ges. We sought to determine whether chronic hypoxia opposes the reduction i n contractile response in uterine and nonuterine vessels during normal preg nancy and, if so, whether decreased basal nitric oxide (NO) activity was in volved. We examined the contractile response to phenylephrine (PE) in guine a pig uterine artery (UA), mesenteric artery (MA), and thoracic aorta (TA) rings isolated from nonpregnant or pregnant guinea pigs that had been expos ed throughout gestation to either low (1,600 m, n = 47) or high (3,962 m, n = 43) altitude. Tn the UA, pregnancy reduced contractile sensitivity to PE and did so similarly at low and high altitude (EC50: 4.0 x 10(-8) nonpregn ant, 9.3 x 10(-8) pregnant at low altitude; 4.8 x 10(-8) nonpregnant, 1.0 x 10(-8) pregnant at high altitude; both P < 0.05). Addition of the NO synth ase inhibitor nitro-L-arginine (NLA; 200 mM) to the vessel bath increased c ontractile sensitivity in the pregnant UA (P < 0.05) and eliminated the eff ect of pregnancy at both altitutes. NLA also raised contractile sensitivity in the nonpregnant high-altitude UA, but contractile response without NLA did not differ in the high- and low-altitude animals. In the MA, pregnancy decreased contractile sensitivity to PE at high altitude only, and this shi ft was reversed by NO inhibition. In the TA, neither pregnancy nor altitude affected contractile response, but NO inhibition raised contractile respon se in nonpregnant and pregnant TA at both altitudes. We concluded that preg nancy diminished contractile response to PE in the UA, likely as a result o f increased NO activity, and that these changes were similar at low and hig h altitude. Counter to our hypothesis, chronic hypoxia did not diminish the pregnancy-associated reduction in contractile sensitivity to PE or inhibit basal NO activity in the UA; rather it enhanced, not diminished, basal NO activity in the nonpregnant UA and the pregnant MA.