Mechanisms of pH preservation during global ischemia in preconditioned rat heart: roles for PKC and NHE - PubMed (original) (raw)
Mechanisms of pH preservation during global ischemia in preconditioned rat heart: roles for PKC and NHE
T F Rehring et al. Am J Physiol. 1998 Sep.
Abstract
Ischemic preconditioning (PC) attenuates cardiac acidosis during global ischemia. This adaptation to ischemia is detectable before other better known indexes of PC are manifested. Clarification of the endogenous mechanisms may provide insights into how protein kinase C (PKC) signaling might be linked to altered intracellular biochemistry. 31P NMR studies of isolated, buffer-perfused rat heart were performed to determine whether functionally cardioprotective PC by cyclic ischemia (CI) and alpha1-adrenergic stimuli [phenylephrine (PE)] attenuated acidosis during ischemia and, if so, whether this 1) involves a PKC-dependent pathway and is due to 2) decreased glycolytic proton production, 3) an increase in proton buffering, or 4) proton extrusion. At the end of 20 min of global ischemia, both CI-PC (pH = 6.86 +/- 0.14) and PE-PC (pH = 6.90 +/- 0.13) attenuated end-ischemic acidosis (control pH = 6.54 +/- 0.1). PKC blockade with chelerythrine (Chel) prevented the attenuation of ischemic acidosis by PC stimuli (end-ischemic pH: CI + Chel, 6.43 +/- 0.06; PE + Chel, 6.17 +/- 0.17). End-ischemic lactate accumulation was decreased in CI-PC hearts (7.54 +/- 0.5 vs. control, 14.61 +/- 2.1 micromol/g wet wt) but not in those preconditioned through the alpha1-adrenergic receptor (12.25 +/- 0.9 micromol/g wet wt). Physiologically relevant buffers were not increased in the preconditioned groups. Blockade of the Na+/H+ exchanger [NHE; with 5-(N-ethyl-N-isopropyl) amiloride (EIPA) or HOE-694] eliminated the attenuation of ischemic acidosis seen with PC stimuli (pH: CI + EIPA, 6.5 +/- 0.1; PE + EIPA, 6.46 +/- 0.2; PE + HOE-694, 6.26 +/- 0.15; not significantly different from control). We conclude that CI and alpha1-adrenergic PC stimuli attenuate ischemic acidosis, and this may involve the cardiac amiloride-sensitive NHE. The signaling pathways of both these two stimuli appear to involve PKC.
Similar articles
- Alpha-adrenergic preservation of myocardial pH during ischemia is PKC isoform dependent.
Rehring TF, Friese RS, Cleveland JC, Meng X, Robertson FG, Harken AH, Bannerjee A. Rehring TF, et al. J Surg Res. 1996 Jun;63(1):324-7. doi: 10.1006/jsre.1996.0269. J Surg Res. 1996. PMID: 8661219 - Short-term inhibition of the Na-H exchanger limits acidosis and reduces ischemic injury in the rat heart.
Schaefer S, Ramasamy R. Schaefer S, et al. Cardiovasc Res. 1997 May;34(2):329-36. doi: 10.1016/s0008-6363(97)00042-4. Cardiovasc Res. 1997. PMID: 9205547 - Comparison of the protective effects of ischemic preconditioning and the Na+/H+ exchanger blockade.
Mosca SM, Cingolani HE. Mosca SM, et al. Naunyn Schmiedebergs Arch Pharmacol. 2000 Jul;362(1):7-13. doi: 10.1007/s002100000255. Naunyn Schmiedebergs Arch Pharmacol. 2000. PMID: 10935527 - Sodium ion/hydrogen ion exchange inhibition: a new pharmacologic approach to myocardial ischemia and reperfusion injury.
Levitsky J, Gurell D, Frishman WH. Levitsky J, et al. J Clin Pharmacol. 1998 Oct;38(10):887-97. doi: 10.1002/j.1552-4604.1998.tb04383.x. J Clin Pharmacol. 1998. PMID: 9807968 Review.
Cited by
- Treatment of acute metabolic acidosis: a pathophysiologic approach.
Kraut JA, Madias NE. Kraut JA, et al. Nat Rev Nephrol. 2012 Oct;8(10):589-601. doi: 10.1038/nrneph.2012.186. Epub 2012 Sep 4. Nat Rev Nephrol. 2012. PMID: 22945490 Review. - Oscillations at odds in the heart.
Weiss JN, Yang JH. Weiss JN, et al. J Gen Physiol. 2010 Apr;135(4):303-5. doi: 10.1085/jgp.201010422. Epub 2010 Mar 15. J Gen Physiol. 2010. PMID: 20231371 Free PMC article. No abstract available. - Glycolytic oscillations in isolated rabbit ventricular myocytes.
Yang JH, Yang L, Qu Z, Weiss JN. Yang JH, et al. J Biol Chem. 2008 Dec 26;283(52):36321-7. doi: 10.1074/jbc.M804794200. Epub 2008 Oct 23. J Biol Chem. 2008. PMID: 18948270 Free PMC article. - Focal adhesion kinase controls pH-dependent epidermal barrier homeostasis by regulating actin-directed Na+/H+ exchanger 1 plasma membrane localization.
Ilic D, Mao-Qiang M, Crumrine D, Dolganov G, Larocque N, Xu P, Demerjian M, Brown BE, Lim ST, Ossovskaya V, Schlaepfer DD, Fisher SJ, Feingold KR, Elias PM, Mauro TM. Ilic D, et al. Am J Pathol. 2007 Jun;170(6):2055-67. doi: 10.2353/ajpath.2007.061277. Am J Pathol. 2007. PMID: 17525272 Free PMC article. - Role of ischaemic preconditioning in liver regeneration following major liver resection and transplantation.
Gomez D, Homer-Vanniasinkam S, Graham AM, Prasad KR. Gomez D, et al. World J Gastroenterol. 2007 Feb 7;13(5):657-70. doi: 10.3748/wjg.v13.i5.657. World J Gastroenterol. 2007. PMID: 17278187 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources