Abstract
Much evidence supports the view that hypoxic/ischemic injury is largely due to increased intracellular Ca concentration ([Ca](i)) resulting from 1) decreased intracellular pH (pH(i)), 2) stimulated Na/H exchange that increases Na uptake and thus intracellular Na (Na(i)), and 3) decreased Na gradient that decreases or reverses net Ca transport via Na/Ca exchange. The Na/H exchanger (NHE) is also stimulated by hypertonic solutions; however, hypertonic media may inhibit NHE's response to changes in pH(i) (Cala PM and Maldonado HM. J Gen Physiol 103: 1035-1054, 1994). Thus we tested the hypothesis that hypertonic perfusion attenuates acid-induced increases in Na(i) in myocardium and, thereby, decreases Ca(i) accumulation during hypoxia. Rabbit hearts were Langendorff perfused with HEPES-buffered Krebs- Henseleit solution equilibrated with 100% O2 or 100% N2. Hypertonic perfusion began 5 min before hypoxia or normoxic acidification (NH4Cl washout). Na(i), [Ca](i), pH(i), and high-energy phosphates were measured by NMR. Control solutions were 295 mosM, and hypertonic solutions were adjusted to 305, 325, or 345 mosM by addition of NaCl or sucrose. During 60 min of hypoxia (295 mosM), Na(i) rose from 22 ± 1 to 100 ± 10 meq/kg dry wt while [Ca](i) rose from 347 ± 11 to 1,306 ± 89 nM. During hypertonic hypoxic perfusion (325 mosM), increases in Na(i) and [Ca](i) were reduced by 65 and 60%, respectively (P < 0.05). Hypertonic perfusion also diminished Na uptake after normoxic acidification by 87% (P < 0.05). The data are consistent with the hypothesis that mild hypertonic perfusion diminishes acid-induced Na accumulation and, thereby, decreases Na/Ca exchange-mediated Ca(i) accumulation during hypoxia.
| Original language | English (US) |
|---|---|
| Journal | American Journal of Physiology - Cell Physiology |
| Volume | 278 |
| Issue number | 5 47-5 |
| State | Published - 2000 |
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Keywords
- Intracellular pH
- Myocardial hypoxia
- Nuclear magnetic resonance spectroscopy
ASJC Scopus subject areas
- Clinical Biochemistry
- Cell Biology
- Physiology
- Physiology (medical)
Cite this
Hypertonic perfusion inhibits intracellular Na and Ca accumulation in hypoxic myocardium. / Ho, Hung S; Liu, Hong; Cala, Peter M; Anderson, Steven E.
In: American Journal of Physiology - Cell Physiology, Vol. 278, No. 5 47-5, 2000.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Hypertonic perfusion inhibits intracellular Na and Ca accumulation in hypoxic myocardium
AU - Ho, Hung S
AU - Liu, Hong
AU - Cala, Peter M
AU - Anderson, Steven E.
PY - 2000
Y1 - 2000
N2 - Much evidence supports the view that hypoxic/ischemic injury is largely due to increased intracellular Ca concentration ([Ca](i)) resulting from 1) decreased intracellular pH (pH(i)), 2) stimulated Na/H exchange that increases Na uptake and thus intracellular Na (Na(i)), and 3) decreased Na gradient that decreases or reverses net Ca transport via Na/Ca exchange. The Na/H exchanger (NHE) is also stimulated by hypertonic solutions; however, hypertonic media may inhibit NHE's response to changes in pH(i) (Cala PM and Maldonado HM. J Gen Physiol 103: 1035-1054, 1994). Thus we tested the hypothesis that hypertonic perfusion attenuates acid-induced increases in Na(i) in myocardium and, thereby, decreases Ca(i) accumulation during hypoxia. Rabbit hearts were Langendorff perfused with HEPES-buffered Krebs- Henseleit solution equilibrated with 100% O2 or 100% N2. Hypertonic perfusion began 5 min before hypoxia or normoxic acidification (NH4Cl washout). Na(i), [Ca](i), pH(i), and high-energy phosphates were measured by NMR. Control solutions were 295 mosM, and hypertonic solutions were adjusted to 305, 325, or 345 mosM by addition of NaCl or sucrose. During 60 min of hypoxia (295 mosM), Na(i) rose from 22 ± 1 to 100 ± 10 meq/kg dry wt while [Ca](i) rose from 347 ± 11 to 1,306 ± 89 nM. During hypertonic hypoxic perfusion (325 mosM), increases in Na(i) and [Ca](i) were reduced by 65 and 60%, respectively (P < 0.05). Hypertonic perfusion also diminished Na uptake after normoxic acidification by 87% (P < 0.05). The data are consistent with the hypothesis that mild hypertonic perfusion diminishes acid-induced Na accumulation and, thereby, decreases Na/Ca exchange-mediated Ca(i) accumulation during hypoxia.
AB - Much evidence supports the view that hypoxic/ischemic injury is largely due to increased intracellular Ca concentration ([Ca](i)) resulting from 1) decreased intracellular pH (pH(i)), 2) stimulated Na/H exchange that increases Na uptake and thus intracellular Na (Na(i)), and 3) decreased Na gradient that decreases or reverses net Ca transport via Na/Ca exchange. The Na/H exchanger (NHE) is also stimulated by hypertonic solutions; however, hypertonic media may inhibit NHE's response to changes in pH(i) (Cala PM and Maldonado HM. J Gen Physiol 103: 1035-1054, 1994). Thus we tested the hypothesis that hypertonic perfusion attenuates acid-induced increases in Na(i) in myocardium and, thereby, decreases Ca(i) accumulation during hypoxia. Rabbit hearts were Langendorff perfused with HEPES-buffered Krebs- Henseleit solution equilibrated with 100% O2 or 100% N2. Hypertonic perfusion began 5 min before hypoxia or normoxic acidification (NH4Cl washout). Na(i), [Ca](i), pH(i), and high-energy phosphates were measured by NMR. Control solutions were 295 mosM, and hypertonic solutions were adjusted to 305, 325, or 345 mosM by addition of NaCl or sucrose. During 60 min of hypoxia (295 mosM), Na(i) rose from 22 ± 1 to 100 ± 10 meq/kg dry wt while [Ca](i) rose from 347 ± 11 to 1,306 ± 89 nM. During hypertonic hypoxic perfusion (325 mosM), increases in Na(i) and [Ca](i) were reduced by 65 and 60%, respectively (P < 0.05). Hypertonic perfusion also diminished Na uptake after normoxic acidification by 87% (P < 0.05). The data are consistent with the hypothesis that mild hypertonic perfusion diminishes acid-induced Na accumulation and, thereby, decreases Na/Ca exchange-mediated Ca(i) accumulation during hypoxia.
KW - Intracellular pH
KW - Myocardial hypoxia
KW - Nuclear magnetic resonance spectroscopy
UR - http://www.scopus.com/inward/record.url?scp=0034041757&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0034041757&partnerID=8YFLogxK
M3 - Article
C2 - 10794669
AN - SCOPUS:0034041757
VL - 278
JO - American Journal of Physiology - Renal Fluid and Electrolyte Physiology
JF - American Journal of Physiology - Renal Fluid and Electrolyte Physiology
SN - 1931-857X
IS - 5 47-5
ER -