Disproportionate Decrease in α- Compared With β-Adrenergic Sensitivity in the Dorsal Hand Vein in Pregnancy Favors Vasodilation

Abstract

Background-Altered vascular responses to adrenergic agonists during pregnancy are thought to play an important role in the regulation of blood pressure and placental blood flow. Because ␣ 1 -adrenergic and ␤ 2 -adrenergic sensitivity act in opposing directions to determine vascular tone, we simultaneously evaluated ␣-adrenergic-mediated vasoconstriction and ␤-adrenergic-mediated vasodilation in dorsal hand veins during and after pregnancy. Methods and Results-Twenty healthy pregnant women were studied at 32 to 37 weeks of gestation and again 12 weeks after delivery. Vascular response to phenylephrine (PE) and isoproterenol (ISO) was measured in a dorsal hand vein using the linear variable differential transformer technique. The dose of PE resulting in 50% constriction (CD 50 ) was determined. The response to ISO was measured after the PE preconstriction. Pregnant and postpartum values, expressed as geometric mean (95% CI), were compared by paired t test. ␣-Adrenergic sensitivity during pregnancy (CD 50 2. Key Words receptors, adrenergic, alpha Ⅲ receptors, adrenergic, beta Ⅲ veins Ⅲ pregnancy Ⅲ vasoconstriction I ntravascular volume is increased substantially in normal pregnancy and is accompanied by decreased arterial and venous tone and blunted vascular responses to vasoconstricting drugs and hormones. 1 Although the alterations in vascular tone and volume are necessary adaptations to the pregnant state, the molecular mechanisms underlying these hemodynamic changes are poorly understood and characterized. It is commonly stated that pregnant women have a diminished response to vasoconstricting and vasodilating drugs and endogenous vasoactive substances, but this phenomenon and its magnitude have rarely been demonstrated in vivo. The dorsal hand-vein technique with a linear variable differential transformer (LVDT) 2 allows the direct, in vivo assessment of vascular responses to a variety of agents. By using low doses of drugs acting primarily at the local segment of the vessel under study, systemic effects and the consequent reflex responses that occur after systemic administration of large doses of vasoactive drugs are avoided, 3,4 making it a particularly attractive method for studying vascular sensitivity during pregnancy. We used the LVDT dorsal hand-vein technique, with infusion of micro-doses of agonists to determine and compare ␣-and ␤-adrenergic vascular sensitivity during normal pregnancy and postpartum. MethodsAfter Institutional Review Board approval and informed written consent, 20 healthy pregnant women were studied. All women were undergoing uncomplicated, singleton pregnancies with no history of significant medical disease or pregnancy-induced hypertension and were taking no medications with the exception of prenatal vitamins. Subjects were studied twice; first between 32 to 37 weeks of gestation and then 12 weeks postpartum. Subjects refrained from cigarette and caffeine consumption for 12 hours before each session, and the studies were performed in a quiet temperature-controlled room. Subjects w...

Magnesium‐induced vasodilation in the dorsal hand vein⋆

“…The mean phenylephrine CD 50 was 733 ng/min (95% CI 241, 2228), consistent with our previous findings in healthy non‐pregnant controls (510 ng/min) and similar to the values we determined in women 12 weeks postpartum (433 ng/min) 7 …”

“…Previous studies have shown that phenylephrine‐induced 50% venoconstriction is stable during this period 10 . The reproducibility of doses–response curves to vasoactive agents has been previously established by others 11 and ourselves in our previous work 7 and has also been demonstrated in other veins such as foot veins 11 …”

“…The dorsal hand vein technique was used as described by Aellig 8,9 and us in our previous work 7 . The study was performed in a quiet temperature‐controlled room and women were studied in the supine position.…”

Attenuated Aortic Vasodilation and Sympathetic Prejunctional Facilitation in Epinephrine-Deficient Mice: Selective Impairment of β2-Adrenoceptor Responses

“…Phenylephrine was selected for precontraction of vascular rings in our experiments because relaxation responses to b-adrenoceptor agonists in vivo occur under tonic constriction caused by a-adrenoceptor stimulation. Both in animals and in humans, changes in the balance of opposing a-and b-adrenoceptor-mediated responses result in alterations of vascular tone in vivo (Landau et al, 2002). No differences were observed between the two experimental groups concerning the degree of contraction induced by the concentration of phenylephrine used (0.3 mM; data not shown).…”

Phenylephrine Infusions during Cesarean Section Under Spinal Anesthesia

“…10 It was believed that the positive inotropic and chronotropic effects of ephedrine raised cardiac output and compensated for its vasoconstrictive effects. 15 Weiner et al 16 showed, in pregnant guinea pig arteries with functional endothelium, significantly reduced sensitivity and response of the uterine artery to the effects of norepinephrine, epinephrine, and phenylephrine, compared with the carotid artery. 11 Support for the preferential use of ephedrine was provided by an in vitro study (sheep blood vessels) demonstrating relative sparing of uterine artery vasoconstriction by ephedrine relative to systemic vessels.…”