In fetal sheep angiotensin II (ANG II)-induced increases in mean arterial pressure (MAP) are mediated through umbilical artery (UA) at1 receptors

J. R. Kaiser, B. E. Cox, C. R. Rosenfeld

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Abstract

ANG II increases MAP dose-dependently in fetal sheep and is important in modulating basal MAP and various fetal stress responses. In adults, systemic vascular smooth muscle (VSM) primarily expresses AT1 receptor subtypes, which mediate vasoconstriction. In contrast, systemic VSM in fetal sheep expresses only AT2 receptors, which do not mediate vasoconstriction. We, however, have observed that the UA expresses only AT1 receptors. Thus we hypothesized that fetal pressor responses to ANG II are primarily, if not solely, due to activation of AT1 receptors in the UA. Fetal sheep (n=5; 125-140d gestation) with chronically implanted flow probes on a femoral artery (only AT2) and UA (only AT1) were studied during systemic ANG II infusions in the absence or presence of AT1 (L158809) and AT, (PD123319) specific antagonists infused directly into the umbilical and hindlimb vascular beds. ANG II (0.229-2.29 μg/min) caused dose-dependent rises (p<0.001) in MAP and UA vascular resistance (UmVR); UA blood flow (UmBF) only fell when the relative rise (%Δ) in UmVR exceeded %Δ MAP. Cumulative doses of L158809 (1 to 125μg infused over 1min) caused dose-dependent inhibition (p<0.001, n=60) of all responses to 1.36±0.10 μg ANG II/min, which results in a 50% rise in MAP: MAP R2=0.76, UmVR R2=0.81 and UmBF R2=0.77. 50% inhibition occurred at 20-25 μg and complete inhibition at ∼100 μg L158809 total dose. Evidence of AT1 inhibition persisted for 48-60h, Importantly, the %Δ in MAP and UmVR were linearly related during AT1 inhibition: R2=0.75, p<0.001, n=60. ANG II did not alter femoral artery blood flow (n=12) either before or during L158809 inhibition. PD123319 (0.5-1000 μg total dose; n=22) infused similarly to L158809 did not affect ANG II-mediated changes in MAP, UmVR or UmBF (R2<0.10). We conclude that ANG II-induced increases in fetal MAP are due solely to increases in UmVR mediated by activation of UA AT1 receptors.

Original languageEnglish (US)
JournalJournal of Investigative Medicine
Volume44
Issue number1
StatePublished - 1996

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Umbilical Arteries
Angiotensin II
Sheep
Arterial Pressure
Femoral Artery
Vasoconstriction
Vascular Smooth Muscle
Muscle
Blood
Chemical activation
Umbilicus
Hindlimb
Vascular Resistance
Blood Vessels
Pregnancy

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

@article{c5832a4e6533492387d57e608679bca6,
title = "In fetal sheep angiotensin II (ANG II)-induced increases in mean arterial pressure (MAP) are mediated through umbilical artery (UA) at1 receptors",
abstract = "ANG II increases MAP dose-dependently in fetal sheep and is important in modulating basal MAP and various fetal stress responses. In adults, systemic vascular smooth muscle (VSM) primarily expresses AT1 receptor subtypes, which mediate vasoconstriction. In contrast, systemic VSM in fetal sheep expresses only AT2 receptors, which do not mediate vasoconstriction. We, however, have observed that the UA expresses only AT1 receptors. Thus we hypothesized that fetal pressor responses to ANG II are primarily, if not solely, due to activation of AT1 receptors in the UA. Fetal sheep (n=5; 125-140d gestation) with chronically implanted flow probes on a femoral artery (only AT2) and UA (only AT1) were studied during systemic ANG II infusions in the absence or presence of AT1 (L158809) and AT, (PD123319) specific antagonists infused directly into the umbilical and hindlimb vascular beds. ANG II (0.229-2.29 μg/min) caused dose-dependent rises (p<0.001) in MAP and UA vascular resistance (UmVR); UA blood flow (UmBF) only fell when the relative rise ({\%}Δ) in UmVR exceeded {\%}Δ MAP. Cumulative doses of L158809 (1 to 125μg infused over 1min) caused dose-dependent inhibition (p<0.001, n=60) of all responses to 1.36±0.10 μg ANG II/min, which results in a 50{\%} rise in MAP: MAP R2=0.76, UmVR R2=0.81 and UmBF R2=0.77. 50{\%} inhibition occurred at 20-25 μg and complete inhibition at ∼100 μg L158809 total dose. Evidence of AT1 inhibition persisted for 48-60h, Importantly, the {\%}Δ in MAP and UmVR were linearly related during AT1 inhibition: R2=0.75, p<0.001, n=60. ANG II did not alter femoral artery blood flow (n=12) either before or during L158809 inhibition. PD123319 (0.5-1000 μg total dose; n=22) infused similarly to L158809 did not affect ANG II-mediated changes in MAP, UmVR or UmBF (R2<0.10). We conclude that ANG II-induced increases in fetal MAP are due solely to increases in UmVR mediated by activation of UA AT1 receptors.",
author = "Kaiser, {J. R.} and Cox, {B. E.} and Rosenfeld, {C. R.}",
year = "1996",
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T1 - In fetal sheep angiotensin II (ANG II)-induced increases in mean arterial pressure (MAP) are mediated through umbilical artery (UA) at1 receptors

AU - Kaiser, J. R.

AU - Cox, B. E.

AU - Rosenfeld, C. R.

PY - 1996

Y1 - 1996

N2 - ANG II increases MAP dose-dependently in fetal sheep and is important in modulating basal MAP and various fetal stress responses. In adults, systemic vascular smooth muscle (VSM) primarily expresses AT1 receptor subtypes, which mediate vasoconstriction. In contrast, systemic VSM in fetal sheep expresses only AT2 receptors, which do not mediate vasoconstriction. We, however, have observed that the UA expresses only AT1 receptors. Thus we hypothesized that fetal pressor responses to ANG II are primarily, if not solely, due to activation of AT1 receptors in the UA. Fetal sheep (n=5; 125-140d gestation) with chronically implanted flow probes on a femoral artery (only AT2) and UA (only AT1) were studied during systemic ANG II infusions in the absence or presence of AT1 (L158809) and AT, (PD123319) specific antagonists infused directly into the umbilical and hindlimb vascular beds. ANG II (0.229-2.29 μg/min) caused dose-dependent rises (p<0.001) in MAP and UA vascular resistance (UmVR); UA blood flow (UmBF) only fell when the relative rise (%Δ) in UmVR exceeded %Δ MAP. Cumulative doses of L158809 (1 to 125μg infused over 1min) caused dose-dependent inhibition (p<0.001, n=60) of all responses to 1.36±0.10 μg ANG II/min, which results in a 50% rise in MAP: MAP R2=0.76, UmVR R2=0.81 and UmBF R2=0.77. 50% inhibition occurred at 20-25 μg and complete inhibition at ∼100 μg L158809 total dose. Evidence of AT1 inhibition persisted for 48-60h, Importantly, the %Δ in MAP and UmVR were linearly related during AT1 inhibition: R2=0.75, p<0.001, n=60. ANG II did not alter femoral artery blood flow (n=12) either before or during L158809 inhibition. PD123319 (0.5-1000 μg total dose; n=22) infused similarly to L158809 did not affect ANG II-mediated changes in MAP, UmVR or UmBF (R2<0.10). We conclude that ANG II-induced increases in fetal MAP are due solely to increases in UmVR mediated by activation of UA AT1 receptors.

AB - ANG II increases MAP dose-dependently in fetal sheep and is important in modulating basal MAP and various fetal stress responses. In adults, systemic vascular smooth muscle (VSM) primarily expresses AT1 receptor subtypes, which mediate vasoconstriction. In contrast, systemic VSM in fetal sheep expresses only AT2 receptors, which do not mediate vasoconstriction. We, however, have observed that the UA expresses only AT1 receptors. Thus we hypothesized that fetal pressor responses to ANG II are primarily, if not solely, due to activation of AT1 receptors in the UA. Fetal sheep (n=5; 125-140d gestation) with chronically implanted flow probes on a femoral artery (only AT2) and UA (only AT1) were studied during systemic ANG II infusions in the absence or presence of AT1 (L158809) and AT, (PD123319) specific antagonists infused directly into the umbilical and hindlimb vascular beds. ANG II (0.229-2.29 μg/min) caused dose-dependent rises (p<0.001) in MAP and UA vascular resistance (UmVR); UA blood flow (UmBF) only fell when the relative rise (%Δ) in UmVR exceeded %Δ MAP. Cumulative doses of L158809 (1 to 125μg infused over 1min) caused dose-dependent inhibition (p<0.001, n=60) of all responses to 1.36±0.10 μg ANG II/min, which results in a 50% rise in MAP: MAP R2=0.76, UmVR R2=0.81 and UmBF R2=0.77. 50% inhibition occurred at 20-25 μg and complete inhibition at ∼100 μg L158809 total dose. Evidence of AT1 inhibition persisted for 48-60h, Importantly, the %Δ in MAP and UmVR were linearly related during AT1 inhibition: R2=0.75, p<0.001, n=60. ANG II did not alter femoral artery blood flow (n=12) either before or during L158809 inhibition. PD123319 (0.5-1000 μg total dose; n=22) infused similarly to L158809 did not affect ANG II-mediated changes in MAP, UmVR or UmBF (R2<0.10). We conclude that ANG II-induced increases in fetal MAP are due solely to increases in UmVR mediated by activation of UA AT1 receptors.

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