Differential development of umbilical and systemic arteries. I. ANG II receptor subtype expression

Jeffrey R. Kaiser, Blair E. Cox, Timothy A. Roy, Charles R. Rosenfeld

Research output: Contribution to journalArticle

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Abstract

In fetal sheep umbilical responses to angiotensin II (ANG II) exceed those by systemic vasculature. Two ANG II receptors (AT) exist, AT1 and AT2, but only AT1 mediates vasoconstriction in adult tissues. Thus differences in reactivity could reflect differences in subtype expression. Using competitive radioligand binding assays, we demonstrated AT1 predominance in umbilical arteries and AT2 in femoral arteries. Steady- state responses to intravenous ANG II (0.229-1.72 μg/min) were studied in 16 fetuses with umbilical and/or femoral artery flow probes without and with local AT1 (L-158,809) or AT2 (PD-123319) blockade. ANG II dose dependently (P < 0.001) increased umbilical resistance more than arterial pressure (MAP) while decreasing umbilical blood flow. Femoral vascular resistance also increased dose dependently (P = 0.02), but responses were less than umbilical (P = 0.0001) and paralleled increases in MAP; blood flow was unaffected. Cumulative local doses of L-158,809 (125 μg) inhibited all responses (P < 0.001); however, 1,000 μg of the AT2 antagonist had no effect. Plasma renin activity (PRA) was unaltered by local AT1 blockade, whereas PRA doubled (P = 0.001) after systemic infusion of only 50 μg of the AT1 antagonist and remained elevated. Differences in umbilical and femoral vascular responses to ANG II are in large part due to differences in AT subtype expression. Furthermore, in fetal sheep the ANG II negative feedback on PRA is mediated by AT1 receptors, and it is substantially more sensitive to receptor blockade than the vasculature.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume274
Issue number3 43-3
StatePublished - Mar 1 1998

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Umbilicus
Umbilical Arteries
Angiotensin Receptors
Angiotensin II
Renin
Femoral Artery
Thigh
Sheep
Arterial Pressure
Radioligand Assay
Competitive Binding
Vasoconstriction
Vascular Resistance
Blood Vessels
Fetus

All Science Journal Classification (ASJC) codes

  • Physiology
  • Physiology (medical)

Cite this

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abstract = "In fetal sheep umbilical responses to angiotensin II (ANG II) exceed those by systemic vasculature. Two ANG II receptors (AT) exist, AT1 and AT2, but only AT1 mediates vasoconstriction in adult tissues. Thus differences in reactivity could reflect differences in subtype expression. Using competitive radioligand binding assays, we demonstrated AT1 predominance in umbilical arteries and AT2 in femoral arteries. Steady- state responses to intravenous ANG II (0.229-1.72 μg/min) were studied in 16 fetuses with umbilical and/or femoral artery flow probes without and with local AT1 (L-158,809) or AT2 (PD-123319) blockade. ANG II dose dependently (P < 0.001) increased umbilical resistance more than arterial pressure (MAP) while decreasing umbilical blood flow. Femoral vascular resistance also increased dose dependently (P = 0.02), but responses were less than umbilical (P = 0.0001) and paralleled increases in MAP; blood flow was unaffected. Cumulative local doses of L-158,809 (125 μg) inhibited all responses (P < 0.001); however, 1,000 μg of the AT2 antagonist had no effect. Plasma renin activity (PRA) was unaltered by local AT1 blockade, whereas PRA doubled (P = 0.001) after systemic infusion of only 50 μg of the AT1 antagonist and remained elevated. Differences in umbilical and femoral vascular responses to ANG II are in large part due to differences in AT subtype expression. Furthermore, in fetal sheep the ANG II negative feedback on PRA is mediated by AT1 receptors, and it is substantially more sensitive to receptor blockade than the vasculature.",
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Differential development of umbilical and systemic arteries. I. ANG II receptor subtype expression. / Kaiser, Jeffrey R.; Cox, Blair E.; Roy, Timothy A.; Rosenfeld, Charles R.

In: American Journal of Physiology - Regulatory Integrative and Comparative Physiology, Vol. 274, No. 3 43-3, 01.03.1998.

Research output: Contribution to journalArticle

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