Angiotensin II triggers EGFR tyrosine kinase-dependent Ca2+ influx in afferent arterioles

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

We previously reported that inhibition of epidermal growth factor receptor tyrosine kinase activity attenuates renal arteriolar contractile responses to angiotensin II. We performed the present experiments to determine if epidermal growth factor receptor tyrosine kinase activity contributes to the afferent arteriolar intracellular [Ca2+] response to angiotensin II. Afferent arterioles were dissected from rat kidney and intracellular [Ca2+] was monitored with the use of fura-2. In normal Ringer's bath containing 1.5 mmol/L Ca2+, basal intracellular [Ca2+] averaged 95±7 nmol/L and 100 nmol/L angiotensin II caused a rapid rise (peak Δ=75±10 nmol/L) that waned to a plateau averaging 24±5 nmol/L above baseline. Pretreatment with 100 nmol/L AG1478 (epidermal growth factor receptor tyrosine kinase inhibitor) reduced both the peak and the plateau stages of the angiotensin II response (peak Δ=42±7 nmol/L; plateau Δ=8±4 nmol/L). A structurally unrelated epidermal growth factor receptor tyrosine kinase inhibitor also suppressed the peak response to angiotensin II, whereas tyrosine phosphatase inhibition enhanced the plateau phase of the response. In the presence of 100 nmol/L extracellular Ca2+, the angiotensin II response was characterized by a peak of diminished magnitude (Δ=49±10 nmol/L; P<0.05 versus the response in normal Ringer's bath) with no plateau, and this response was unaffected by AG1478. Moreover, angiotensin II stimulation of divalent cation influx (Mn2+ quench of fura-2 fluorescence) was decreased significantly by AG1478. We conclude that epidermal growth factor receptor tyrosine kinase activity contributes to the afferent arteriolar intracellular [Ca2+] response to angiotensin II and that this process involves promotion of Ca2+ influx.

Original languageEnglish (US)
Pages (from-to)700-706
Number of pages7
JournalHypertension
Volume40
Issue number5
DOIs
StatePublished - Nov 1 2002

Fingerprint

Arterioles
Angiotensin II
Protein-Tyrosine Kinases
Epidermal Growth Factor Receptor
Baths
Kidney
Fura-2
Divalent Cations
Phosphoric Monoester Hydrolases
Tyrosine
Fluorescence
tyrphostin AG 1478

Keywords

  • Angiotensin
  • Calcium
  • Epidermal growth factor
  • Muscle, smooth vascular
  • Protein kinases
  • Renal circulation

ASJC Scopus subject areas

  • Internal Medicine

Cite this

Angiotensin II triggers EGFR tyrosine kinase-dependent Ca2+ influx in afferent arterioles. / Che, Qi; Carmines, Pamela K.

In: Hypertension, Vol. 40, No. 5, 01.11.2002, p. 700-706.

Research output: Contribution to journalArticle

@article{52bac6675b574bbe8b327b0432fd8151,
title = "Angiotensin II triggers EGFR tyrosine kinase-dependent Ca2+ influx in afferent arterioles",
abstract = "We previously reported that inhibition of epidermal growth factor receptor tyrosine kinase activity attenuates renal arteriolar contractile responses to angiotensin II. We performed the present experiments to determine if epidermal growth factor receptor tyrosine kinase activity contributes to the afferent arteriolar intracellular [Ca2+] response to angiotensin II. Afferent arterioles were dissected from rat kidney and intracellular [Ca2+] was monitored with the use of fura-2. In normal Ringer's bath containing 1.5 mmol/L Ca2+, basal intracellular [Ca2+] averaged 95±7 nmol/L and 100 nmol/L angiotensin II caused a rapid rise (peak Δ=75±10 nmol/L) that waned to a plateau averaging 24±5 nmol/L above baseline. Pretreatment with 100 nmol/L AG1478 (epidermal growth factor receptor tyrosine kinase inhibitor) reduced both the peak and the plateau stages of the angiotensin II response (peak Δ=42±7 nmol/L; plateau Δ=8±4 nmol/L). A structurally unrelated epidermal growth factor receptor tyrosine kinase inhibitor also suppressed the peak response to angiotensin II, whereas tyrosine phosphatase inhibition enhanced the plateau phase of the response. In the presence of 100 nmol/L extracellular Ca2+, the angiotensin II response was characterized by a peak of diminished magnitude (Δ=49±10 nmol/L; P<0.05 versus the response in normal Ringer's bath) with no plateau, and this response was unaffected by AG1478. Moreover, angiotensin II stimulation of divalent cation influx (Mn2+ quench of fura-2 fluorescence) was decreased significantly by AG1478. We conclude that epidermal growth factor receptor tyrosine kinase activity contributes to the afferent arteriolar intracellular [Ca2+] response to angiotensin II and that this process involves promotion of Ca2+ influx.",
keywords = "Angiotensin, Calcium, Epidermal growth factor, Muscle, smooth vascular, Protein kinases, Renal circulation",
author = "Qi Che and Carmines, {Pamela K}",
year = "2002",
month = "11",
day = "1",
doi = "10.1161/01.HYP.0000035524.10948.93",
language = "English (US)",
volume = "40",
pages = "700--706",
journal = "Hypertension",
issn = "0194-911X",
publisher = "Lippincott Williams and Wilkins",
number = "5",

}

TY - JOUR

T1 - Angiotensin II triggers EGFR tyrosine kinase-dependent Ca2+ influx in afferent arterioles

AU - Che, Qi

AU - Carmines, Pamela K

PY - 2002/11/1

Y1 - 2002/11/1

N2 - We previously reported that inhibition of epidermal growth factor receptor tyrosine kinase activity attenuates renal arteriolar contractile responses to angiotensin II. We performed the present experiments to determine if epidermal growth factor receptor tyrosine kinase activity contributes to the afferent arteriolar intracellular [Ca2+] response to angiotensin II. Afferent arterioles were dissected from rat kidney and intracellular [Ca2+] was monitored with the use of fura-2. In normal Ringer's bath containing 1.5 mmol/L Ca2+, basal intracellular [Ca2+] averaged 95±7 nmol/L and 100 nmol/L angiotensin II caused a rapid rise (peak Δ=75±10 nmol/L) that waned to a plateau averaging 24±5 nmol/L above baseline. Pretreatment with 100 nmol/L AG1478 (epidermal growth factor receptor tyrosine kinase inhibitor) reduced both the peak and the plateau stages of the angiotensin II response (peak Δ=42±7 nmol/L; plateau Δ=8±4 nmol/L). A structurally unrelated epidermal growth factor receptor tyrosine kinase inhibitor also suppressed the peak response to angiotensin II, whereas tyrosine phosphatase inhibition enhanced the plateau phase of the response. In the presence of 100 nmol/L extracellular Ca2+, the angiotensin II response was characterized by a peak of diminished magnitude (Δ=49±10 nmol/L; P<0.05 versus the response in normal Ringer's bath) with no plateau, and this response was unaffected by AG1478. Moreover, angiotensin II stimulation of divalent cation influx (Mn2+ quench of fura-2 fluorescence) was decreased significantly by AG1478. We conclude that epidermal growth factor receptor tyrosine kinase activity contributes to the afferent arteriolar intracellular [Ca2+] response to angiotensin II and that this process involves promotion of Ca2+ influx.

AB - We previously reported that inhibition of epidermal growth factor receptor tyrosine kinase activity attenuates renal arteriolar contractile responses to angiotensin II. We performed the present experiments to determine if epidermal growth factor receptor tyrosine kinase activity contributes to the afferent arteriolar intracellular [Ca2+] response to angiotensin II. Afferent arterioles were dissected from rat kidney and intracellular [Ca2+] was monitored with the use of fura-2. In normal Ringer's bath containing 1.5 mmol/L Ca2+, basal intracellular [Ca2+] averaged 95±7 nmol/L and 100 nmol/L angiotensin II caused a rapid rise (peak Δ=75±10 nmol/L) that waned to a plateau averaging 24±5 nmol/L above baseline. Pretreatment with 100 nmol/L AG1478 (epidermal growth factor receptor tyrosine kinase inhibitor) reduced both the peak and the plateau stages of the angiotensin II response (peak Δ=42±7 nmol/L; plateau Δ=8±4 nmol/L). A structurally unrelated epidermal growth factor receptor tyrosine kinase inhibitor also suppressed the peak response to angiotensin II, whereas tyrosine phosphatase inhibition enhanced the plateau phase of the response. In the presence of 100 nmol/L extracellular Ca2+, the angiotensin II response was characterized by a peak of diminished magnitude (Δ=49±10 nmol/L; P<0.05 versus the response in normal Ringer's bath) with no plateau, and this response was unaffected by AG1478. Moreover, angiotensin II stimulation of divalent cation influx (Mn2+ quench of fura-2 fluorescence) was decreased significantly by AG1478. We conclude that epidermal growth factor receptor tyrosine kinase activity contributes to the afferent arteriolar intracellular [Ca2+] response to angiotensin II and that this process involves promotion of Ca2+ influx.

KW - Angiotensin

KW - Calcium

KW - Epidermal growth factor

KW - Muscle, smooth vascular

KW - Protein kinases

KW - Renal circulation

UR - http://www.scopus.com/inward/record.url?scp=0036840894&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036840894&partnerID=8YFLogxK

U2 - 10.1161/01.HYP.0000035524.10948.93

DO - 10.1161/01.HYP.0000035524.10948.93

M3 - Article

C2 - 12411465

AN - SCOPUS:0036840894

VL - 40

SP - 700

EP - 706

JO - Hypertension

JF - Hypertension

SN - 0194-911X

IS - 5

ER -