Endogenous modulation of the blunted adrenergic response in resistance-sized mesenteric arteries from the pregnant rat Sandra T. Davidge, MS, and Margaret K. McLaughlin, PhD
Cincinnati, Ohio OBJECTIVE: We tested the hypothesis that during pregnancy the endothelium mediates the blunted response to adrenergic vasoconstriction. STUDY DESIGN: Mesenteric resistance arteries from late pregnant (n = 6) and age-matched virgin control (n = 6) Sprague-Dawley rats were studied in a myograph. RESULTS: Arteries from pregnant rats were 35% less sensitive to phenylephrine vasoconstriction than were those from nonpregnant rats (mean effective concentration that produced a 50% response 2.26 vs 1.48 Il-mol/L, pregnant vs nonpregnant, p < 0.01). Meclofenamate had no effect on the vasoconstrictor response in arteries from either group. Inhibition of endothelium-derived relaxing factor with W-nitro-L-arginine methyl ester or endothelial cell removal had a similar twofold increase in phenylephrine sensitivity in arteries from both the pregnant and nonpregnant rats (mean effective concentration that produced a 50% response 2.26 vs 1.11 Il-mol/L for pregnant rats and 1.48 vs 0.72 Il-mol/L for nonpregnant rats, p < 0.01). However, methacholine relaxation response was potentiated in pregnant versus nonpregnant rats (mean effective concentration that produced a 50% response 0.030 vs 0.049 Il-mol/L, p < 0.01). CONCLUSION: Although the potential for endothelium-dependent relaxation is augmented in mesenteric arteries of the pregnant rat, the decreased sensitivity to phenylephrine during pregnancy is not modulated acutely by endothelium-derived relaxing factor or by prostaglandin products of the cyclooxygenase pathway. (AM J OSSTET GYNECOL 1992;167:1691-8.)
Key words: Pregnancy, adrenergic vascular reactivity, resistance arteries, endothelium, Sprague-Dawley rat The maternal hemodynamics of normal pregnancy have been well described. This includes the decrease in peripheral vascular resistance that is associated with a decreased pressor responsiveness to vasoconstrictors. I This reduction in vascular reactivity is clinically important because it is not evident in women with pregnancyinduced hypertension or preeclampsia. 2 In spite of considerable research the mechanisms that could account for this decreased pressor responsiveness during pregnancy are not well understood. Specific alterations within the vascular wall are likely to contribute significantly to this gestational change in vascular reactivity. The endothelium produces and releases substances such as prostacyclin and endothelium-derived From the Perinatal Research Institute, Division of Neonatology, Department of Pediatrics, University of Cincinnati College of Medicine. Supported in part by United States Public Health Service grant No. 40130.
Presented at the Thirty-ninth Annual Meeting of the Society for Gynecologic Investigation, San Antonio, Texas, March 18-21, 1992. Reprint requests: Margaret K. McLaughlin, PhD, Children's Hospital Medical Center, TCHRF - Neonatology Division, Eiland and Bethesda Ave., Cincinnati, OH 45229-2899. 6/6/41903
relaxing factor (EDRF) that will modulate the constriction of vascular smooth muscle. 3 However, it remains controversial if these vasorelaxants are involved in the decreased vasoreactivity observed during pregnancy.
Cincinnati, Ohio OBJECTIVE: We tested the hypothesis that during pregnancy the endothelium mediates the blunted response to adrenergic vasoconstriction. STUDY DESIGN: Mesenteric resistance arteries from late pregnant (n = 6) and age-matched virgin control (n = 6) Sprague-Dawley rats were studied in a myograph. RESULTS: Arteries from pregnant rats were 35% less sensitive to phenylephrine vasoconstriction than were those from nonpregnant rats (mean effective concentration that produced a 50% response 2.26 vs 1.48 Il-mol/L, pregnant vs nonpregnant, p < 0.01). Meclofenamate had no effect on the vasoconstrictor response in arteries from either group. Inhibition of endothelium-derived relaxing factor with W-nitro-L-arginine methyl ester or endothelial cell removal had a similar twofold increase in phenylephrine sensitivity in arteries from both the pregnant and nonpregnant rats (mean effective concentration that produced a 50% response 2.26 vs 1.11 Il-mol/L for pregnant rats and 1.48 vs 0.72 Il-mol/L for nonpregnant rats, p < 0.01). However, methacholine relaxation response was potentiated in pregnant versus nonpregnant rats (mean effective concentration that produced a 50% response 0.030 vs 0.049 Il-mol/L, p < 0.01). CONCLUSION: Although the potential for endothelium-dependent relaxation is augmented in mesenteric arteries of the pregnant rat, the decreased sensitivity to phenylephrine during pregnancy is not modulated acutely by endothelium-derived relaxing factor or by prostaglandin products of the cyclooxygenase pathway. (AM J OSSTET GYNECOL 1992;167:1691-8.)
Key words: Pregnancy, adrenergic vascular reactivity, resistance arteries, endothelium, Sprague-Dawley rat The maternal hemodynamics of normal pregnancy have been well described. This includes the decrease in peripheral vascular resistance that is associated with a decreased pressor responsiveness to vasoconstrictors. I This reduction in vascular reactivity is clinically important because it is not evident in women with pregnancyinduced hypertension or preeclampsia. 2 In spite of considerable research the mechanisms that could account for this decreased pressor responsiveness during pregnancy are not well understood. Specific alterations within the vascular wall are likely to contribute significantly to this gestational change in vascular reactivity. The endothelium produces and releases substances such as prostacyclin and endothelium-derived From the Perinatal Research Institute, Division of Neonatology, Department of Pediatrics, University of Cincinnati College of Medicine. Supported in part by United States Public Health Service grant No. 40130.
Presented at the Thirty-ninth Annual Meeting of the Society for Gynecologic Investigation, San Antonio, Texas, March 18-21, 1992. Reprint requests: Margaret K. McLaughlin, PhD, Children's Hospital Medical Center, TCHRF - Neonatology Division, Eiland and Bethesda Ave., Cincinnati, OH 45229-2899. 6/6/41903
relaxing factor (EDRF) that will modulate the constriction of vascular smooth muscle. 3 However, it remains controversial if these vasorelaxants are involved in the decreased vasoreactivity observed during pregnancy.
