Amiloride delays the ischemia-induced rise in cytosolic free calcium

E. Murphy, M. Perlman, R. E. London, Charles Jr Steenbergen

Research output: Contribution to journalArticle

Abstract

An increase in cytosolic free calcium (Ca(i)) has been shown to occur early during ischemia in perfused rat, ferret, and rabbit hearts. It has been proposed that this increase in Ca(i) may occur as a result of exchange of Na(i) for Ca(o), which occurs as a result of an increase in Na(i) arising from exchange of Na(o) for H+(i). The latter exchange is stimulated by the intracellular acidification that occurs during ischemia. To test this hypothesis, we examined Ca(i), Na(i), ATP, and pH(i) during ischemia in rats in the presence and absence of 1 mM amiloride, a Na-H exchange inhibitor. Ca(i) was measured using 19F nuclear magnetic resonance (NMR) of 1,2-bis(2-amino-5-fluorophenoxy)ethane-N,N,N',N'-tetra-acetic acid (5F-BAPTA)-loaded rat hearts. Na(i) was measured using 23Na NMR, and the shift reagent 1, 4, 7, 10-tetraazacyclododecane-N,N',N'',N'''-tetramethylenephosphonate (Tm[DOTP]-5) was used to separate Na(i) and Na(o). ATP and pH were determined from 31P NMR measurements. During 20 minutes of ischemia, amiloride did not significantly alter the ATP decline but did significantly attenuate the rise in Na(i) and Ca(i). After 20 minutes of ischemia, time-averaged Ca(i) was 1.0±0.2 μM (mean±SEM) in amiloride-treated hearts compared with 2.3±0.9 μM in nontreated hearts. After 20 minutes of ischemia, Na(i) in the untreated heart was threefold greater than control, whereas in the amiloride-treated heart, Na(i) was not significantly different from control. These data are consistent with the involvement of Na-Ca exchange in the rise in Ca(i) during ischemia. In addition, recovery of contractile function during reperfusion after 20 minutes of ischemia was significantly better in amiloride-treated hearts (71±10%) than in nontreated hearts (24±13%). These data are consistent with the hypothesis suggesting that the elevation in Ca(i) during ischemia may contribute to postischemic contractile dysfunction.

Original languageEnglish (US)
Pages (from-to)1250-1258
Number of pages9
JournalCirculation Research
Volume68
Issue number5
StatePublished - 1991
Externally publishedYes

Fingerprint

Amiloride
Ischemia
Calcium
Magnetic Resonance Spectroscopy
Adenosine Triphosphate
Ferrets
Ethane
Recovery of Function
Acetic Acid
Reperfusion
Rabbits

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Amiloride delays the ischemia-induced rise in cytosolic free calcium. / Murphy, E.; Perlman, M.; London, R. E.; Steenbergen, Charles Jr.

In: Circulation Research, Vol. 68, No. 5, 1991, p. 1250-1258.

Research output: Contribution to journalArticle

Murphy, E, Perlman, M, London, RE & Steenbergen, CJ 1991, 'Amiloride delays the ischemia-induced rise in cytosolic free calcium', Circulation Research, vol. 68, no. 5, pp. 1250-1258.
Murphy, E. ; Perlman, M. ; London, R. E. ; Steenbergen, Charles Jr. / Amiloride delays the ischemia-induced rise in cytosolic free calcium. In: Circulation Research. 1991 ; Vol. 68, No. 5. pp. 1250-1258.
@article{b2afbd1c2dd04c86b4a73b7bf2e3e471,
title = "Amiloride delays the ischemia-induced rise in cytosolic free calcium",
abstract = "An increase in cytosolic free calcium (Ca(i)) has been shown to occur early during ischemia in perfused rat, ferret, and rabbit hearts. It has been proposed that this increase in Ca(i) may occur as a result of exchange of Na(i) for Ca(o), which occurs as a result of an increase in Na(i) arising from exchange of Na(o) for H+(i). The latter exchange is stimulated by the intracellular acidification that occurs during ischemia. To test this hypothesis, we examined Ca(i), Na(i), ATP, and pH(i) during ischemia in rats in the presence and absence of 1 mM amiloride, a Na-H exchange inhibitor. Ca(i) was measured using 19F nuclear magnetic resonance (NMR) of 1,2-bis(2-amino-5-fluorophenoxy)ethane-N,N,N',N'-tetra-acetic acid (5F-BAPTA)-loaded rat hearts. Na(i) was measured using 23Na NMR, and the shift reagent 1, 4, 7, 10-tetraazacyclododecane-N,N',N'',N'''-tetramethylenephosphonate (Tm[DOTP]-5) was used to separate Na(i) and Na(o). ATP and pH were determined from 31P NMR measurements. During 20 minutes of ischemia, amiloride did not significantly alter the ATP decline but did significantly attenuate the rise in Na(i) and Ca(i). After 20 minutes of ischemia, time-averaged Ca(i) was 1.0±0.2 μM (mean±SEM) in amiloride-treated hearts compared with 2.3±0.9 μM in nontreated hearts. After 20 minutes of ischemia, Na(i) in the untreated heart was threefold greater than control, whereas in the amiloride-treated heart, Na(i) was not significantly different from control. These data are consistent with the involvement of Na-Ca exchange in the rise in Ca(i) during ischemia. In addition, recovery of contractile function during reperfusion after 20 minutes of ischemia was significantly better in amiloride-treated hearts (71±10{\%}) than in nontreated hearts (24±13{\%}). These data are consistent with the hypothesis suggesting that the elevation in Ca(i) during ischemia may contribute to postischemic contractile dysfunction.",
author = "E. Murphy and M. Perlman and London, {R. E.} and Steenbergen, {Charles Jr}",
year = "1991",
language = "English (US)",
volume = "68",
pages = "1250--1258",
journal = "Circulation Research",
issn = "0009-7330",
publisher = "Lippincott Williams and Wilkins",
number = "5",

}

TY - JOUR

T1 - Amiloride delays the ischemia-induced rise in cytosolic free calcium

AU - Murphy, E.

AU - Perlman, M.

AU - London, R. E.

AU - Steenbergen, Charles Jr

PY - 1991

Y1 - 1991

N2 - An increase in cytosolic free calcium (Ca(i)) has been shown to occur early during ischemia in perfused rat, ferret, and rabbit hearts. It has been proposed that this increase in Ca(i) may occur as a result of exchange of Na(i) for Ca(o), which occurs as a result of an increase in Na(i) arising from exchange of Na(o) for H+(i). The latter exchange is stimulated by the intracellular acidification that occurs during ischemia. To test this hypothesis, we examined Ca(i), Na(i), ATP, and pH(i) during ischemia in rats in the presence and absence of 1 mM amiloride, a Na-H exchange inhibitor. Ca(i) was measured using 19F nuclear magnetic resonance (NMR) of 1,2-bis(2-amino-5-fluorophenoxy)ethane-N,N,N',N'-tetra-acetic acid (5F-BAPTA)-loaded rat hearts. Na(i) was measured using 23Na NMR, and the shift reagent 1, 4, 7, 10-tetraazacyclododecane-N,N',N'',N'''-tetramethylenephosphonate (Tm[DOTP]-5) was used to separate Na(i) and Na(o). ATP and pH were determined from 31P NMR measurements. During 20 minutes of ischemia, amiloride did not significantly alter the ATP decline but did significantly attenuate the rise in Na(i) and Ca(i). After 20 minutes of ischemia, time-averaged Ca(i) was 1.0±0.2 μM (mean±SEM) in amiloride-treated hearts compared with 2.3±0.9 μM in nontreated hearts. After 20 minutes of ischemia, Na(i) in the untreated heart was threefold greater than control, whereas in the amiloride-treated heart, Na(i) was not significantly different from control. These data are consistent with the involvement of Na-Ca exchange in the rise in Ca(i) during ischemia. In addition, recovery of contractile function during reperfusion after 20 minutes of ischemia was significantly better in amiloride-treated hearts (71±10%) than in nontreated hearts (24±13%). These data are consistent with the hypothesis suggesting that the elevation in Ca(i) during ischemia may contribute to postischemic contractile dysfunction.

AB - An increase in cytosolic free calcium (Ca(i)) has been shown to occur early during ischemia in perfused rat, ferret, and rabbit hearts. It has been proposed that this increase in Ca(i) may occur as a result of exchange of Na(i) for Ca(o), which occurs as a result of an increase in Na(i) arising from exchange of Na(o) for H+(i). The latter exchange is stimulated by the intracellular acidification that occurs during ischemia. To test this hypothesis, we examined Ca(i), Na(i), ATP, and pH(i) during ischemia in rats in the presence and absence of 1 mM amiloride, a Na-H exchange inhibitor. Ca(i) was measured using 19F nuclear magnetic resonance (NMR) of 1,2-bis(2-amino-5-fluorophenoxy)ethane-N,N,N',N'-tetra-acetic acid (5F-BAPTA)-loaded rat hearts. Na(i) was measured using 23Na NMR, and the shift reagent 1, 4, 7, 10-tetraazacyclododecane-N,N',N'',N'''-tetramethylenephosphonate (Tm[DOTP]-5) was used to separate Na(i) and Na(o). ATP and pH were determined from 31P NMR measurements. During 20 minutes of ischemia, amiloride did not significantly alter the ATP decline but did significantly attenuate the rise in Na(i) and Ca(i). After 20 minutes of ischemia, time-averaged Ca(i) was 1.0±0.2 μM (mean±SEM) in amiloride-treated hearts compared with 2.3±0.9 μM in nontreated hearts. After 20 minutes of ischemia, Na(i) in the untreated heart was threefold greater than control, whereas in the amiloride-treated heart, Na(i) was not significantly different from control. These data are consistent with the involvement of Na-Ca exchange in the rise in Ca(i) during ischemia. In addition, recovery of contractile function during reperfusion after 20 minutes of ischemia was significantly better in amiloride-treated hearts (71±10%) than in nontreated hearts (24±13%). These data are consistent with the hypothesis suggesting that the elevation in Ca(i) during ischemia may contribute to postischemic contractile dysfunction.

UR - http://www.scopus.com/inward/record.url?scp=0025726641&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0025726641&partnerID=8YFLogxK

M3 - Article

VL - 68

SP - 1250

EP - 1258

JO - Circulation Research

JF - Circulation Research

SN - 0009-7330

IS - 5

ER -