Selective antagonism of the AT(1) receptor inhibits angiotensin II stimulated DNA and protein synthesis in primary cultures of human proximal tubular cells

P K Chatterjee, R P Weerackody, S K Mistry, G M Hawksworth, J S McLay

Research output: Contribution to journalArticle

Abstract

The hypertrophy of renal proximal tubular cells occurs as an adaptive response to a variety of stimuli and may be involved with the progression of renal disease. Angiotensin II, acting alone or in combination with other growth factors has been implicated in this process. The aims of this study were to identify the role of both angiotensin II and the angiotensin receptor subtypes in DNA synthesis and protein synthesis in human renal proximal tubular cells. Primary cultures of human renal proximal tubular cells were incubated with angiotensin II (10(-10) M, 10(-8) M, 10(-6) M) for 24 to 120 hours either alone or in combination with losartan, PD123319 or 8-bromo-cAMP. Incubation of human proximal tubular cells with angiotensin II (10(-10) M, 10(-8) M) induced a significant early increase in [H-3]thymidine uptake by 19% and 56% (P < 0.01), respectively, and a later increase in total protein content by 30% (P < 0.01). The effect of angiotensin II upon DNA and protein synthesis was inhibited by 8-bromo-cAMP and losartan but not by PD123319, indicating that the responses are mediated via the AT, receptor and dependent upon the inhibition of adenylate cyclase.

Original languageEnglish
Pages (from-to)699-705
Number of pages7
JournalKidney International
Volume52
Issue number3
Publication statusPublished - Sep 1997

Keywords

  • angiotensin II
  • losartan
  • PD 123319
  • DNA synthesis
  • protein synthesis
  • AT(1) receptor
  • GROWTH-FACTOR-BETA
  • CELLULAR HYPERTROPHY
  • RENAL GROWTH
  • RAT-KIDNEY
  • PROLIFERATION
  • COLLAGEN

Cite this

Selective antagonism of the AT(1) receptor inhibits angiotensin II stimulated DNA and protein synthesis in primary cultures of human proximal tubular cells. / Chatterjee, P K ; Weerackody, R P ; Mistry, S K ; Hawksworth, G M ; McLay, J S .

In: Kidney International, Vol. 52, No. 3, 09.1997, p. 699-705.

Research output: Contribution to journalArticle

@article{9d43f7ad885642d6bbfd539350f20163,
title = "Selective antagonism of the AT(1) receptor inhibits angiotensin II stimulated DNA and protein synthesis in primary cultures of human proximal tubular cells",
abstract = "The hypertrophy of renal proximal tubular cells occurs as an adaptive response to a variety of stimuli and may be involved with the progression of renal disease. Angiotensin II, acting alone or in combination with other growth factors has been implicated in this process. The aims of this study were to identify the role of both angiotensin II and the angiotensin receptor subtypes in DNA synthesis and protein synthesis in human renal proximal tubular cells. Primary cultures of human renal proximal tubular cells were incubated with angiotensin II (10(-10) M, 10(-8) M, 10(-6) M) for 24 to 120 hours either alone or in combination with losartan, PD123319 or 8-bromo-cAMP. Incubation of human proximal tubular cells with angiotensin II (10(-10) M, 10(-8) M) induced a significant early increase in [H-3]thymidine uptake by 19{\%} and 56{\%} (P < 0.01), respectively, and a later increase in total protein content by 30{\%} (P < 0.01). The effect of angiotensin II upon DNA and protein synthesis was inhibited by 8-bromo-cAMP and losartan but not by PD123319, indicating that the responses are mediated via the AT, receptor and dependent upon the inhibition of adenylate cyclase.",
keywords = "angiotensin II, losartan, PD 123319, DNA synthesis, protein synthesis, AT(1) receptor, GROWTH-FACTOR-BETA, CELLULAR HYPERTROPHY, RENAL GROWTH, RAT-KIDNEY, PROLIFERATION, COLLAGEN",
author = "Chatterjee, {P K} and Weerackody, {R P} and Mistry, {S K} and Hawksworth, {G M} and McLay, {J S}",
year = "1997",
month = "9",
language = "English",
volume = "52",
pages = "699--705",
journal = "Kidney International",
issn = "0085-2538",
publisher = "Nature Publishing Group",
number = "3",

}

TY - JOUR

T1 - Selective antagonism of the AT(1) receptor inhibits angiotensin II stimulated DNA and protein synthesis in primary cultures of human proximal tubular cells

AU - Chatterjee, P K

AU - Weerackody, R P

AU - Mistry, S K

AU - Hawksworth, G M

AU - McLay, J S

PY - 1997/9

Y1 - 1997/9

N2 - The hypertrophy of renal proximal tubular cells occurs as an adaptive response to a variety of stimuli and may be involved with the progression of renal disease. Angiotensin II, acting alone or in combination with other growth factors has been implicated in this process. The aims of this study were to identify the role of both angiotensin II and the angiotensin receptor subtypes in DNA synthesis and protein synthesis in human renal proximal tubular cells. Primary cultures of human renal proximal tubular cells were incubated with angiotensin II (10(-10) M, 10(-8) M, 10(-6) M) for 24 to 120 hours either alone or in combination with losartan, PD123319 or 8-bromo-cAMP. Incubation of human proximal tubular cells with angiotensin II (10(-10) M, 10(-8) M) induced a significant early increase in [H-3]thymidine uptake by 19% and 56% (P < 0.01), respectively, and a later increase in total protein content by 30% (P < 0.01). The effect of angiotensin II upon DNA and protein synthesis was inhibited by 8-bromo-cAMP and losartan but not by PD123319, indicating that the responses are mediated via the AT, receptor and dependent upon the inhibition of adenylate cyclase.

AB - The hypertrophy of renal proximal tubular cells occurs as an adaptive response to a variety of stimuli and may be involved with the progression of renal disease. Angiotensin II, acting alone or in combination with other growth factors has been implicated in this process. The aims of this study were to identify the role of both angiotensin II and the angiotensin receptor subtypes in DNA synthesis and protein synthesis in human renal proximal tubular cells. Primary cultures of human renal proximal tubular cells were incubated with angiotensin II (10(-10) M, 10(-8) M, 10(-6) M) for 24 to 120 hours either alone or in combination with losartan, PD123319 or 8-bromo-cAMP. Incubation of human proximal tubular cells with angiotensin II (10(-10) M, 10(-8) M) induced a significant early increase in [H-3]thymidine uptake by 19% and 56% (P < 0.01), respectively, and a later increase in total protein content by 30% (P < 0.01). The effect of angiotensin II upon DNA and protein synthesis was inhibited by 8-bromo-cAMP and losartan but not by PD123319, indicating that the responses are mediated via the AT, receptor and dependent upon the inhibition of adenylate cyclase.

KW - angiotensin II

KW - losartan

KW - PD 123319

KW - DNA synthesis

KW - protein synthesis

KW - AT(1) receptor

KW - GROWTH-FACTOR-BETA

KW - CELLULAR HYPERTROPHY

KW - RENAL GROWTH

KW - RAT-KIDNEY

KW - PROLIFERATION

KW - COLLAGEN

M3 - Article

VL - 52

SP - 699

EP - 705

JO - Kidney International

JF - Kidney International

SN - 0085-2538

IS - 3

ER -