Tissue specific expression of vascular smooth muscle angiotensin II receptor subtypes during ovine pregnancy

Blair E. Cox, Charles R. Rosenfeld, Judith E. Kalinyak, Ronald R. Magness, Philip W. Shaul

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44 Citations (Scopus)

Abstract

Uteroplacental responses to infused angiotensin II (ANG II) are less than those elicited by systemic vasculature. This does not reflect ANGII receptor (AT) downregulation but may reflect differences in AT-receptor subtypes expressed. We examined AT-receptor subtypes in smooth muscle (SM) from uterine (UA), mesenteric, renal, and mammary arteries and aorta from nulliparous (n = 12), pregnant (n = 18; 105-140 days, term = 145 days), postpartum (n = 5; 6-9 days after delivery), and nonpregnant parous (n = 14) ewes by assessing displacement of 125I-labeled ANG II binding by [Sar1,Ile8]ANG II (AT1 and AT2), losartan (AT1), PD-123319 (AT2), and CGP-42112A (AT2). AT2 receptors accounted for 75-90% of total binding in UA. Except for mammary arteries, other arteries expressed only AT1 receptors. Receptor subtype expression was not altered by reproductive state in any artery studied. With the use of autoradiography, AT2 receptors appear to predominate in media of small intramyometrial arteries, whereas AT1 receptors predominate in the luminal portion. We therefore determined which subtype mediates endothelium-derived ANG II-induced increases in UA PGI2 synthesis during pregnancy. ANGII (0.05 μM) increased PGI2 synthesis 62%, from 214 ± 13 to 346 ± 23 pg·mg-1·h-1 (P < 0.05). Losartan (1.0 μM) inhibited the rise in PGI2 (257 ± 24 vs. 238 ± 25 pg·mg-1·h-1), whereas 1.0 μM PD-123319 had no effect (231 ± 23 vs. 337 ± 31 pg·mg-1·h-1; P < 0.05). AT2 receptors do not mediate ANG II-induced vasoconstriction, thus differences in uteroplacental and systemic sensitivity to ANG II may reflect predominance of AT2 receptors in UA SM and ANG II-induced increases in UA prostacyclin synthesis by endothelial AT1 receptors.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume40
Issue number1
StatePublished - Jul 1996

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Angiotensin Receptors
Vascular Smooth Muscle
Angiotensin II
Sheep
Pregnancy
Epoprostenol
Mammary Arteries
Losartan
Arteries
Smooth Muscle
Uterine Artery
Mesenteric Arteries
Renal Artery
Vasoconstriction
Autoradiography
Postpartum Period
Endothelium
Aorta
Down-Regulation

Keywords

  • Endothelium
  • Mammary artery
  • Prostacyclin
  • Puerperium
  • Uteroplacental circulation

ASJC Scopus subject areas

  • Physiology

Cite this

@article{f36e2f6070fc4c6c9f1c1e4d7cbc3af7,
title = "Tissue specific expression of vascular smooth muscle angiotensin II receptor subtypes during ovine pregnancy",
abstract = "Uteroplacental responses to infused angiotensin II (ANG II) are less than those elicited by systemic vasculature. This does not reflect ANGII receptor (AT) downregulation but may reflect differences in AT-receptor subtypes expressed. We examined AT-receptor subtypes in smooth muscle (SM) from uterine (UA), mesenteric, renal, and mammary arteries and aorta from nulliparous (n = 12), pregnant (n = 18; 105-140 days, term = 145 days), postpartum (n = 5; 6-9 days after delivery), and nonpregnant parous (n = 14) ewes by assessing displacement of 125I-labeled ANG II binding by [Sar1,Ile8]ANG II (AT1 and AT2), losartan (AT1), PD-123319 (AT2), and CGP-42112A (AT2). AT2 receptors accounted for 75-90{\%} of total binding in UA. Except for mammary arteries, other arteries expressed only AT1 receptors. Receptor subtype expression was not altered by reproductive state in any artery studied. With the use of autoradiography, AT2 receptors appear to predominate in media of small intramyometrial arteries, whereas AT1 receptors predominate in the luminal portion. We therefore determined which subtype mediates endothelium-derived ANG II-induced increases in UA PGI2 synthesis during pregnancy. ANGII (0.05 μM) increased PGI2 synthesis 62{\%}, from 214 ± 13 to 346 ± 23 pg·mg-1·h-1 (P < 0.05). Losartan (1.0 μM) inhibited the rise in PGI2 (257 ± 24 vs. 238 ± 25 pg·mg-1·h-1), whereas 1.0 μM PD-123319 had no effect (231 ± 23 vs. 337 ± 31 pg·mg-1·h-1; P < 0.05). AT2 receptors do not mediate ANG II-induced vasoconstriction, thus differences in uteroplacental and systemic sensitivity to ANG II may reflect predominance of AT2 receptors in UA SM and ANG II-induced increases in UA prostacyclin synthesis by endothelial AT1 receptors.",
keywords = "Endothelium, Mammary artery, Prostacyclin, Puerperium, Uteroplacental circulation",
author = "Cox, {Blair E.} and Rosenfeld, {Charles R.} and Kalinyak, {Judith E.} and Magness, {Ronald R.} and Shaul, {Philip W.}",
year = "1996",
month = "7",
language = "English (US)",
volume = "40",
journal = "American Journal of Physiology - Heart and Circulatory Physiology",
issn = "0363-6135",
publisher = "American Physiological Society",
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TY - JOUR

T1 - Tissue specific expression of vascular smooth muscle angiotensin II receptor subtypes during ovine pregnancy

AU - Cox, Blair E.

AU - Rosenfeld, Charles R.

AU - Kalinyak, Judith E.

AU - Magness, Ronald R.

AU - Shaul, Philip W.

PY - 1996/7

Y1 - 1996/7

N2 - Uteroplacental responses to infused angiotensin II (ANG II) are less than those elicited by systemic vasculature. This does not reflect ANGII receptor (AT) downregulation but may reflect differences in AT-receptor subtypes expressed. We examined AT-receptor subtypes in smooth muscle (SM) from uterine (UA), mesenteric, renal, and mammary arteries and aorta from nulliparous (n = 12), pregnant (n = 18; 105-140 days, term = 145 days), postpartum (n = 5; 6-9 days after delivery), and nonpregnant parous (n = 14) ewes by assessing displacement of 125I-labeled ANG II binding by [Sar1,Ile8]ANG II (AT1 and AT2), losartan (AT1), PD-123319 (AT2), and CGP-42112A (AT2). AT2 receptors accounted for 75-90% of total binding in UA. Except for mammary arteries, other arteries expressed only AT1 receptors. Receptor subtype expression was not altered by reproductive state in any artery studied. With the use of autoradiography, AT2 receptors appear to predominate in media of small intramyometrial arteries, whereas AT1 receptors predominate in the luminal portion. We therefore determined which subtype mediates endothelium-derived ANG II-induced increases in UA PGI2 synthesis during pregnancy. ANGII (0.05 μM) increased PGI2 synthesis 62%, from 214 ± 13 to 346 ± 23 pg·mg-1·h-1 (P < 0.05). Losartan (1.0 μM) inhibited the rise in PGI2 (257 ± 24 vs. 238 ± 25 pg·mg-1·h-1), whereas 1.0 μM PD-123319 had no effect (231 ± 23 vs. 337 ± 31 pg·mg-1·h-1; P < 0.05). AT2 receptors do not mediate ANG II-induced vasoconstriction, thus differences in uteroplacental and systemic sensitivity to ANG II may reflect predominance of AT2 receptors in UA SM and ANG II-induced increases in UA prostacyclin synthesis by endothelial AT1 receptors.

AB - Uteroplacental responses to infused angiotensin II (ANG II) are less than those elicited by systemic vasculature. This does not reflect ANGII receptor (AT) downregulation but may reflect differences in AT-receptor subtypes expressed. We examined AT-receptor subtypes in smooth muscle (SM) from uterine (UA), mesenteric, renal, and mammary arteries and aorta from nulliparous (n = 12), pregnant (n = 18; 105-140 days, term = 145 days), postpartum (n = 5; 6-9 days after delivery), and nonpregnant parous (n = 14) ewes by assessing displacement of 125I-labeled ANG II binding by [Sar1,Ile8]ANG II (AT1 and AT2), losartan (AT1), PD-123319 (AT2), and CGP-42112A (AT2). AT2 receptors accounted for 75-90% of total binding in UA. Except for mammary arteries, other arteries expressed only AT1 receptors. Receptor subtype expression was not altered by reproductive state in any artery studied. With the use of autoradiography, AT2 receptors appear to predominate in media of small intramyometrial arteries, whereas AT1 receptors predominate in the luminal portion. We therefore determined which subtype mediates endothelium-derived ANG II-induced increases in UA PGI2 synthesis during pregnancy. ANGII (0.05 μM) increased PGI2 synthesis 62%, from 214 ± 13 to 346 ± 23 pg·mg-1·h-1 (P < 0.05). Losartan (1.0 μM) inhibited the rise in PGI2 (257 ± 24 vs. 238 ± 25 pg·mg-1·h-1), whereas 1.0 μM PD-123319 had no effect (231 ± 23 vs. 337 ± 31 pg·mg-1·h-1; P < 0.05). AT2 receptors do not mediate ANG II-induced vasoconstriction, thus differences in uteroplacental and systemic sensitivity to ANG II may reflect predominance of AT2 receptors in UA SM and ANG II-induced increases in UA prostacyclin synthesis by endothelial AT1 receptors.

KW - Endothelium

KW - Mammary artery

KW - Prostacyclin

KW - Puerperium

KW - Uteroplacental circulation

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