Alterations in vasoconstrictor responses to the endothelium-derived contracting factor uridine adenosine tetraphosphate are region specific in DOCA-salt hypertensive rats

Takayuki Matsumoto, Rita C. Tostes, R Clinton Webb

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Uridine adenosine tetraphosphate (Up 4A) has been recently identified as a novel and potent endothelium-derived contracting factor and contains both purine and pyrimidine moieties, which activate purinergic P2X and P2Y receptors. The present study was designed to compare contractile responses to Up 4A and other nucleotides such as ATP (P2X/P2Y agonist), UTP (P2Y 2/P2Y 4 agonist), UDP (P2Y 6 agonist), and α,β-methylene ATP (P2X 1 agonist) in different vascular regions [thoracic aorta, basilar, small mesenteric, and femoral arteries] from deoxycorticosterone acetate-salt (DOCA-salt) and control rats. In DOCA-salt rats [vs. control uninephrectomized (Uni) rats]: (1) in thoracic aorta, Up 4A-, ATP-, and UTP-induced contractions were unchanged; (2) in basilar artery, Up 4A-, ATP-, UTP- and UDP-induced contractions were increased, and expression for P2X 1, but not P2Y 2 or P2Y 6 was decreased; (3) in small mesenteric artery, Up 4A-induced contraction was decreased and UDP-induced contraction was increased; expression of P2Y 2 and P2X 1 was decreased whereas P2Y 6 expression was increased; (4) in femoral artery, Up 4A-, UTP-, and UDP-induced contractions were increased, but expression of P2Y 2, P2Y 6 and P2X 1 was unchanged. The α,β-methylene ATP-induced contraction was bell-shaped and the maximal contraction was reached at a lower concentration in basilar and mesenteric arteries from Uni rats, compared to arteries from DOCA-salt rats. These results suggest that Up 4A-induced contraction is heterogenously affected among various vascular beds in arterial hypertension. P2Y receptor activation may contribute to enhancement of Up 4A-induced contraction in basilar and femoral arteries. These changes in vascular reactivity to Up 4A may be adaptive to the vascular alterations produced by hypertension.

Original languageEnglish (US)
Pages (from-to)81-90
Number of pages10
JournalPharmacological Research
Volume65
Issue number1
DOIs
StatePublished - Jan 1 2012

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Desoxycorticosterone
Vasoconstrictor Agents
Uridine Triphosphate
Endothelium
Acetates
Salts
Adenosine Triphosphate
Basilar Artery
Mesenteric Arteries
Uridine Diphosphate
Blood Vessels
Femoral Artery
Thoracic Aorta
Purinergic P2Y Receptors
Purinergic P2X Receptors
Hypertension
Nucleotides
Arteries
uridine adenosine tetraphosphate

Keywords

  • Contraction
  • DOCA-salt
  • Dinucleotide
  • EDCF
  • Extracellular nucleotides
  • P2 receptor

ASJC Scopus subject areas

  • Pharmacology

Cite this

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title = "Alterations in vasoconstrictor responses to the endothelium-derived contracting factor uridine adenosine tetraphosphate are region specific in DOCA-salt hypertensive rats",
abstract = "Uridine adenosine tetraphosphate (Up 4A) has been recently identified as a novel and potent endothelium-derived contracting factor and contains both purine and pyrimidine moieties, which activate purinergic P2X and P2Y receptors. The present study was designed to compare contractile responses to Up 4A and other nucleotides such as ATP (P2X/P2Y agonist), UTP (P2Y 2/P2Y 4 agonist), UDP (P2Y 6 agonist), and α,β-methylene ATP (P2X 1 agonist) in different vascular regions [thoracic aorta, basilar, small mesenteric, and femoral arteries] from deoxycorticosterone acetate-salt (DOCA-salt) and control rats. In DOCA-salt rats [vs. control uninephrectomized (Uni) rats]: (1) in thoracic aorta, Up 4A-, ATP-, and UTP-induced contractions were unchanged; (2) in basilar artery, Up 4A-, ATP-, UTP- and UDP-induced contractions were increased, and expression for P2X 1, but not P2Y 2 or P2Y 6 was decreased; (3) in small mesenteric artery, Up 4A-induced contraction was decreased and UDP-induced contraction was increased; expression of P2Y 2 and P2X 1 was decreased whereas P2Y 6 expression was increased; (4) in femoral artery, Up 4A-, UTP-, and UDP-induced contractions were increased, but expression of P2Y 2, P2Y 6 and P2X 1 was unchanged. The α,β-methylene ATP-induced contraction was bell-shaped and the maximal contraction was reached at a lower concentration in basilar and mesenteric arteries from Uni rats, compared to arteries from DOCA-salt rats. These results suggest that Up 4A-induced contraction is heterogenously affected among various vascular beds in arterial hypertension. P2Y receptor activation may contribute to enhancement of Up 4A-induced contraction in basilar and femoral arteries. These changes in vascular reactivity to Up 4A may be adaptive to the vascular alterations produced by hypertension.",
keywords = "Contraction, DOCA-salt, Dinucleotide, EDCF, Extracellular nucleotides, P2 receptor",
author = "Takayuki Matsumoto and Tostes, {Rita C.} and Webb, {R Clinton}",
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T1 - Alterations in vasoconstrictor responses to the endothelium-derived contracting factor uridine adenosine tetraphosphate are region specific in DOCA-salt hypertensive rats

AU - Matsumoto, Takayuki

AU - Tostes, Rita C.

AU - Webb, R Clinton

PY - 2012/1/1

Y1 - 2012/1/1

N2 - Uridine adenosine tetraphosphate (Up 4A) has been recently identified as a novel and potent endothelium-derived contracting factor and contains both purine and pyrimidine moieties, which activate purinergic P2X and P2Y receptors. The present study was designed to compare contractile responses to Up 4A and other nucleotides such as ATP (P2X/P2Y agonist), UTP (P2Y 2/P2Y 4 agonist), UDP (P2Y 6 agonist), and α,β-methylene ATP (P2X 1 agonist) in different vascular regions [thoracic aorta, basilar, small mesenteric, and femoral arteries] from deoxycorticosterone acetate-salt (DOCA-salt) and control rats. In DOCA-salt rats [vs. control uninephrectomized (Uni) rats]: (1) in thoracic aorta, Up 4A-, ATP-, and UTP-induced contractions were unchanged; (2) in basilar artery, Up 4A-, ATP-, UTP- and UDP-induced contractions were increased, and expression for P2X 1, but not P2Y 2 or P2Y 6 was decreased; (3) in small mesenteric artery, Up 4A-induced contraction was decreased and UDP-induced contraction was increased; expression of P2Y 2 and P2X 1 was decreased whereas P2Y 6 expression was increased; (4) in femoral artery, Up 4A-, UTP-, and UDP-induced contractions were increased, but expression of P2Y 2, P2Y 6 and P2X 1 was unchanged. The α,β-methylene ATP-induced contraction was bell-shaped and the maximal contraction was reached at a lower concentration in basilar and mesenteric arteries from Uni rats, compared to arteries from DOCA-salt rats. These results suggest that Up 4A-induced contraction is heterogenously affected among various vascular beds in arterial hypertension. P2Y receptor activation may contribute to enhancement of Up 4A-induced contraction in basilar and femoral arteries. These changes in vascular reactivity to Up 4A may be adaptive to the vascular alterations produced by hypertension.

AB - Uridine adenosine tetraphosphate (Up 4A) has been recently identified as a novel and potent endothelium-derived contracting factor and contains both purine and pyrimidine moieties, which activate purinergic P2X and P2Y receptors. The present study was designed to compare contractile responses to Up 4A and other nucleotides such as ATP (P2X/P2Y agonist), UTP (P2Y 2/P2Y 4 agonist), UDP (P2Y 6 agonist), and α,β-methylene ATP (P2X 1 agonist) in different vascular regions [thoracic aorta, basilar, small mesenteric, and femoral arteries] from deoxycorticosterone acetate-salt (DOCA-salt) and control rats. In DOCA-salt rats [vs. control uninephrectomized (Uni) rats]: (1) in thoracic aorta, Up 4A-, ATP-, and UTP-induced contractions were unchanged; (2) in basilar artery, Up 4A-, ATP-, UTP- and UDP-induced contractions were increased, and expression for P2X 1, but not P2Y 2 or P2Y 6 was decreased; (3) in small mesenteric artery, Up 4A-induced contraction was decreased and UDP-induced contraction was increased; expression of P2Y 2 and P2X 1 was decreased whereas P2Y 6 expression was increased; (4) in femoral artery, Up 4A-, UTP-, and UDP-induced contractions were increased, but expression of P2Y 2, P2Y 6 and P2X 1 was unchanged. The α,β-methylene ATP-induced contraction was bell-shaped and the maximal contraction was reached at a lower concentration in basilar and mesenteric arteries from Uni rats, compared to arteries from DOCA-salt rats. These results suggest that Up 4A-induced contraction is heterogenously affected among various vascular beds in arterial hypertension. P2Y receptor activation may contribute to enhancement of Up 4A-induced contraction in basilar and femoral arteries. These changes in vascular reactivity to Up 4A may be adaptive to the vascular alterations produced by hypertension.

KW - Contraction

KW - DOCA-salt

KW - Dinucleotide

KW - EDCF

KW - Extracellular nucleotides

KW - P2 receptor

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U2 - 10.1016/j.phrs.2011.09.005

DO - 10.1016/j.phrs.2011.09.005

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JO - Pharmacological Research

JF - Pharmacological Research

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