Gestational resistance to the pulmonary vasoconstrictor effect of the TxA2 mimetic U-46619: Possible mechanism

G. Losonczy, G. Brown, I. Muchá, R. Klocke, V. Müller, B. Merkely, L. Tornoci, L. Rosivall, R. Venuto

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Pregnancy is associated with the reduction of vascular sensitivity to vasoconstrictor compounds. We have examined whether pregnancy in rabbits induces hyposensitivity of the pulmonary vascular system to U-46619. Anesthetized, mechanically ventilated nonpregnant (NP; n = 7) and late- pregnant (P; n = 7) rabbits were studied. The intravenous injection of 0.03, 0.1, and 0.3 μg/kg U-46619 led to a dose-dependent elevation of mean pulmonary arterial pressure (MPAP) in NP rabbits from a baseline value of 15 ± 1 to 22 ± 1 mgHg. There was no significant MPAP response to intravenous administration of U-46619 in P rabbits. The pulmonary arterial pressure response of isolated, ventilated, and buffer-perfused lungs of P rabbits was also blunted (P <0.001 vs. NP). Pulmonary arterial membrane binding of [125I]BOP, another thromboxane (Tx)A2 analog, indicated 48 ± 16 fmol receptors/mg protein in P rabbits and 193 ± 48 fmol receptors/mg protein in NP samples (P <0.025). Receptor affinity [1/dissociation constant (K(D))] was also lower in the tissue of P rabbits (P <0.01 vs. NP). The urinary excretion of the stable TxA2 metabolite 11-dehydro-TxB2 was lower in P than in NP rabbits (P <0.02), which made homologous desensitization an unlikely explanation for the changes of vascular TxA2 receptors. These results show that, in late gestation, rabbit pulmonary vascular sensitivity to U-46619 is reduced simultaneously with, and as a possible consequence of, downregulation of specific receptors.

Original languageEnglish
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume272
Issue number6 41-6
Publication statusPublished - 1997

Fingerprint

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
Vasoconstrictor Agents
Rabbits
Lung
Blood Vessels
Arterial Pressure
Pregnancy
Thromboxane A2
Intravenous Injections
Intravenous Administration
Buffers
Proteins
Down-Regulation
Membranes

Keywords

  • Preeclampsia
  • Pulmonary hypertension
  • Thromboxane receptors
  • Vascular reactivity

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

@article{b5b78d40f6414b39bac694463c17179e,
title = "Gestational resistance to the pulmonary vasoconstrictor effect of the TxA2 mimetic U-46619: Possible mechanism",
abstract = "Pregnancy is associated with the reduction of vascular sensitivity to vasoconstrictor compounds. We have examined whether pregnancy in rabbits induces hyposensitivity of the pulmonary vascular system to U-46619. Anesthetized, mechanically ventilated nonpregnant (NP; n = 7) and late- pregnant (P; n = 7) rabbits were studied. The intravenous injection of 0.03, 0.1, and 0.3 μg/kg U-46619 led to a dose-dependent elevation of mean pulmonary arterial pressure (MPAP) in NP rabbits from a baseline value of 15 ± 1 to 22 ± 1 mgHg. There was no significant MPAP response to intravenous administration of U-46619 in P rabbits. The pulmonary arterial pressure response of isolated, ventilated, and buffer-perfused lungs of P rabbits was also blunted (P <0.001 vs. NP). Pulmonary arterial membrane binding of [125I]BOP, another thromboxane (Tx)A2 analog, indicated 48 ± 16 fmol receptors/mg protein in P rabbits and 193 ± 48 fmol receptors/mg protein in NP samples (P <0.025). Receptor affinity [1/dissociation constant (K(D))] was also lower in the tissue of P rabbits (P <0.01 vs. NP). The urinary excretion of the stable TxA2 metabolite 11-dehydro-TxB2 was lower in P than in NP rabbits (P <0.02), which made homologous desensitization an unlikely explanation for the changes of vascular TxA2 receptors. These results show that, in late gestation, rabbit pulmonary vascular sensitivity to U-46619 is reduced simultaneously with, and as a possible consequence of, downregulation of specific receptors.",
keywords = "Preeclampsia, Pulmonary hypertension, Thromboxane receptors, Vascular reactivity",
author = "G. Losonczy and G. Brown and I. Much{\'a} and R. Klocke and V. M{\"u}ller and B. Merkely and L. Tornoci and L. Rosivall and R. Venuto",
year = "1997",
language = "English",
volume = "272",
journal = "American Journal of Physiology",
issn = "0363-6119",
publisher = "American Physiological Society",
number = "6 41-6",

}

TY - JOUR

T1 - Gestational resistance to the pulmonary vasoconstrictor effect of the TxA2 mimetic U-46619

T2 - Possible mechanism

AU - Losonczy, G.

AU - Brown, G.

AU - Muchá, I.

AU - Klocke, R.

AU - Müller, V.

AU - Merkely, B.

AU - Tornoci, L.

AU - Rosivall, L.

AU - Venuto, R.

PY - 1997

Y1 - 1997

N2 - Pregnancy is associated with the reduction of vascular sensitivity to vasoconstrictor compounds. We have examined whether pregnancy in rabbits induces hyposensitivity of the pulmonary vascular system to U-46619. Anesthetized, mechanically ventilated nonpregnant (NP; n = 7) and late- pregnant (P; n = 7) rabbits were studied. The intravenous injection of 0.03, 0.1, and 0.3 μg/kg U-46619 led to a dose-dependent elevation of mean pulmonary arterial pressure (MPAP) in NP rabbits from a baseline value of 15 ± 1 to 22 ± 1 mgHg. There was no significant MPAP response to intravenous administration of U-46619 in P rabbits. The pulmonary arterial pressure response of isolated, ventilated, and buffer-perfused lungs of P rabbits was also blunted (P <0.001 vs. NP). Pulmonary arterial membrane binding of [125I]BOP, another thromboxane (Tx)A2 analog, indicated 48 ± 16 fmol receptors/mg protein in P rabbits and 193 ± 48 fmol receptors/mg protein in NP samples (P <0.025). Receptor affinity [1/dissociation constant (K(D))] was also lower in the tissue of P rabbits (P <0.01 vs. NP). The urinary excretion of the stable TxA2 metabolite 11-dehydro-TxB2 was lower in P than in NP rabbits (P <0.02), which made homologous desensitization an unlikely explanation for the changes of vascular TxA2 receptors. These results show that, in late gestation, rabbit pulmonary vascular sensitivity to U-46619 is reduced simultaneously with, and as a possible consequence of, downregulation of specific receptors.

AB - Pregnancy is associated with the reduction of vascular sensitivity to vasoconstrictor compounds. We have examined whether pregnancy in rabbits induces hyposensitivity of the pulmonary vascular system to U-46619. Anesthetized, mechanically ventilated nonpregnant (NP; n = 7) and late- pregnant (P; n = 7) rabbits were studied. The intravenous injection of 0.03, 0.1, and 0.3 μg/kg U-46619 led to a dose-dependent elevation of mean pulmonary arterial pressure (MPAP) in NP rabbits from a baseline value of 15 ± 1 to 22 ± 1 mgHg. There was no significant MPAP response to intravenous administration of U-46619 in P rabbits. The pulmonary arterial pressure response of isolated, ventilated, and buffer-perfused lungs of P rabbits was also blunted (P <0.001 vs. NP). Pulmonary arterial membrane binding of [125I]BOP, another thromboxane (Tx)A2 analog, indicated 48 ± 16 fmol receptors/mg protein in P rabbits and 193 ± 48 fmol receptors/mg protein in NP samples (P <0.025). Receptor affinity [1/dissociation constant (K(D))] was also lower in the tissue of P rabbits (P <0.01 vs. NP). The urinary excretion of the stable TxA2 metabolite 11-dehydro-TxB2 was lower in P than in NP rabbits (P <0.02), which made homologous desensitization an unlikely explanation for the changes of vascular TxA2 receptors. These results show that, in late gestation, rabbit pulmonary vascular sensitivity to U-46619 is reduced simultaneously with, and as a possible consequence of, downregulation of specific receptors.

KW - Preeclampsia

KW - Pulmonary hypertension

KW - Thromboxane receptors

KW - Vascular reactivity

UR - http://www.scopus.com/inward/record.url?scp=0030790893&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030790893&partnerID=8YFLogxK

M3 - Article

C2 - 9227584

AN - SCOPUS:0030790893

VL - 272

JO - American Journal of Physiology

JF - American Journal of Physiology

SN - 0363-6119

IS - 6 41-6

ER -