Differential effects of angiotensin AT1and AT2receptors on the expression, translation and function of the Na+-H+exchanger and Na+-HCO3−symporter in the rat heart after myocardial infarction

Sandmann, Steffen; Yu, Minghuan; Kaschina, Elena; Blume, Annegret; Bouzinova, Elena V.; Aalkjær, Christian; Unger, Thomas

doi:10.1016/s0735-1097(01)01287-6

Cited by 62 publications

(31 citation statements)

References 49 publications

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“…Previous studies have also reported increased mRNA expression of NBC associated with cardiac pathology. For example, Sandmann et al (33) reported that mRNA levels of NBC-1 (NBCe) were increased twofold in the rat LV FW after myocardial infarction. In human cardiomyopathic hearts (i.e., ischemic and dilated cardiomyopathy), Khandoudi et al (21) demonstrated that hhNBC (NBCe1) mRNA expression increased, whereas mRNA level of NBCn remained unchanged.…”

Section: Discussionmentioning

confidence: 99%

Enhanced activity of ventricular Na⁺-HCO₃⁻ cotransport in pressure overload hypertrophy

Yamamoto¹,

Shirayama²,

Sakatani³

et al. 2007

American Journal of Physiology-Heart and Circulatory Physiology

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The Na(+)-HCO(3)(-) cotransporter (NBC) plays a key role in intracellular pH (pH(i)) regulation in normal ventricular muscle. However, the state of NBC in nonischemic hypertrophied hearts is unresolved. In this study, we examined functional and molecular properties of NBC in adult rat ventricular myocytes. The cells were enzymatically isolated from both normal and hypertrophied hearts. Ventricular hypertrophy was induced by pressure overload created by suprarenal abdominal aortic constriction of 50% for 7 wk. pH(i) was measured in single cells using the fluorescent pH indicator 2',7'-bis(2-carboxyethyl)5-(6)carboxyfluorescein. Real-time PCR analysis was used to quantitatively assess expression of NBC-encoding mRNA, including SLC4A4 (encoding electrogenic NBC, NBCe1) and SLC4A7 (electroneutral NBC, NBCn1). Our results demonstrate that: 1) mRNA levels of both the electrogenic NBCe1 (SLC4A4) and electroneutral NBCn1 (SLC4A7) forms of NBC were increased by aortic constriction, 2) the onset of NBC upregulation occurred within 3 days after constriction, 3) normal and hypertrophied ventricles displayed regional differences in NBC expression, 4) acid extrusion via NBC (J(NBC)) was increased significantly in hypertrophied myocytes, 5) although acid extrusion via Na(+)/H(+) exchange was also increased in hypertrophied myocytes, the relative enhancement of J(NBC) was larger, 6) membrane depolarization markedly increased J(NBC) in hypertrophied myocytes, and 7) losartan, an ANG II AT(1) receptor antagonist, significantly attenuated the upregulation of both NBCs induced by 3 wk of aortic constriction. Enhanced NBC activity during hypertrophic development provides a mechanism for intracellular Na(+) overload, which may render the ventricles more vulnerable to Ca(2+) overload during ischemia-reperfusion.

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Section: Discussionmentioning

confidence: 99%

Enhanced activity of ventricular Na⁺-HCO₃⁻ cotransport in pressure overload hypertrophy

Yamamoto¹,

Shirayama²,

Sakatani³

et al. 2007

American Journal of Physiology-Heart and Circulatory Physiology

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“…NBCe1 is expressed in the heart, although at a lower abundance than in kidney or pancreas (6,31,140,192,480,684,831). Full-length NBCe1-B has been cloned from human heart cDNA (192), and an antibody directed against the third extracellular loop of NBCe1 immunoreacts with protein in rat and human ventricular myocardial cells (481).…”

Section: V) Circulatory System A) Heart Most Northern Blot Analysesmentioning

confidence: 99%

The Divergence, Actions, Roles, and Relatives of Sodium-Coupled Bicarbonate Transporters

Parker

Boron

2013

Physiological Reviews

246

262

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The mammalian Slc4 (Solute carrier 4) family of transporters is a functionally diverse group of 10 multi-spanning membrane proteins that includes three Cl-HCO3 exchangers (AE1-3), five Na(+)-coupled HCO3(-) transporters (NCBTs), and two other unusual members (AE4, BTR1). In this review, we mainly focus on the five mammalian NCBTs-NBCe1, NBCe2, NBCn1, NDCBE, and NBCn2. Each plays a specialized role in maintaining intracellular pH and, by contributing to the movement of HCO3(-) across epithelia, in maintaining whole-body pH and otherwise contributing to epithelial transport. Disruptions involving NCBT genes are linked to blindness, deafness, proximal renal tubular acidosis, mental retardation, and epilepsy. We also review AE1-3, AE4, and BTR1, addressing their relevance to the study of NCBTs. This review draws together recent advances in our understanding of the phylogenetic origins and physiological relevance of NCBTs and their progenitors. Underlying these advances is progress in such diverse disciplines as physiology, molecular biology, genetics, immunocytochemistry, proteomics, and structural biology. This review highlights the key similarities and differences between individual NCBTs and the genes that encode them and also clarifies the sometimes confusing NCBT nomenclature.

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“…Myocardial ischemia-induced acidification (11,35) and the presence of an endogenous agonist such as ANG II may obviously represent stimulatory events for NBC activity. From our earlier results (19), it was clear that an HCO 3 Ϫ -dependent mechanism contributed to pH i recovery after ischemia in adult rat hearts.…”

Section: Regulation Of Sarcolemmal Nbc Activity By Ang IImentioning

confidence: 99%

The ERK pathway regulates Na⁺-HCO 3 − cotransport activity in adult rat cardiomyocytes

Baetz

Haworth

Avkiran

et al. 2002

American Journal of Physiology-Heart and Circulatory Physiology

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Baetz, Delphine, Robert S. Haworth, Metin Avkiran, and Danielle Feuvray. The ERK pathway regulates Na ϩ -HCO 3 Ϫ cotransport activity in adult rat cardiomyocytes. Am J Physiol Heart Circ Physiol 283: H2102-H2109, 2002. First published July 11, 2002; 10.1152/ajpheart.01071.2001.-The sarcolemmal Na ϩ -HCO 3 Ϫ cotransporter (NBC) is stimulated by intracellular acidification and acts as an acid extruder. We examined the role of the ERK pathway of the MAPK cascade as a potential mediator of NBC activation by intracellular acidification in the presence and absence of angiotensin II (ANG II) in adult rat ventricular myocytes. Intracellular pH (pH i) was recorded with the use of seminaphthorhodafluor-1. The NH 4 ϩ method was used to induce an intracellular acid load. NBC activation was significantly decreased with the ERK inhibitors PD-98059 and U-0126. NBC activity after acidification was increased in the presence of ANG II (pH i range of 6.75-7.00). ANG II plus PD-123319 (AT2 antagonist) still increased NBC activity, whereas ANG II plus losartan (AT 1 antagonist) did not affect it. ERK phosphorylation (measured by immunoblot analysis) during intracellular acidification was increased by ANG II, an effect that was abolished by losartan and U-0126. In conclusion, the MAP-K(ERK)-dependent pathway facilitates the rate of pHi recovery from acid load through NBC activity and is involved in the AT1 receptor-mediated stimulation of such activity by ANG II. cardiac ventricular myocytes; angiotensin II THE ISOFORM Na ϩ -HCO 3 Ϫ cotransporter (NBC) was recently cloned from cardiac tissue (9), and functional studies (1,8,9,22,24,41) have provided evidence that it is stimulated by intracellular acidification and acts as an acid extruder. In a previous study, we (24) showed that NBC activity, besides that of the Na ϩ /H ϩ exchanger, accounted for ϳ38% of the total acid efflux from ventricular myocytes of normal adult rats after intracellular acidification at intracellular pH (pH i ) 6.8. Increased sarcolemmal NBC activity and consequent increases in pH i and Na ϩ have been suggested to be causally involved in pathophysiological responses, notably during ischemia and/or reperfusion (19). However, little is known about the signal transduction mechanisms that cause NBC activation and that might regulate its activity. In contrast to the reported role for intracellular Ca 2ϩ in the control of Na ϩ /H ϩ exchange activity (the other major pH i alkalinizing transporter) (23), the activity of NBC was not affected by decreasing intracellular Ca 2ϩ or by inhibiting Ca 2ϩ /calmodulin protein kinase II (24). In cultured neonatal rat ventricular myocytes, angiotensin II (ANG II) was shown to activate the NBC and the results of the study (21) supported the view that the consequent increase in pH i was independent of the ANG type 1 (AT 1 ) receptor phosphoinositide signaling pathway. They suggested that the AT 2 signaling pathway may underlie the response.Both AT 1 and AT 2 subtypes of the ANG II receptor are expressed in the ventricular myocardium...

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Differential effects of angiotensin AT1and AT2receptors on the expression, translation and function of the Na+-H+exchanger and Na+-HCO3−symporter in the rat heart after myocardial infarction

Abstract: Angiotensin II via its AT1 and AT2 receptors differentially controls transcriptional and translational regulation as well as the activity of NHE-1 and NBC-1 in the ischemic myocardium and contributes to the control of pH regulation in cardiac tissue.

Cited by 62 publications

References 49 publications

Enhanced activity of ventricular Na⁺-HCO₃⁻ cotransport in pressure overload hypertrophy

Enhanced activity of ventricular Na⁺-HCO₃⁻ cotransport in pressure overload hypertrophy

The Divergence, Actions, Roles, and Relatives of Sodium-Coupled Bicarbonate Transporters

The ERK pathway regulates Na⁺-HCO 3 − cotransport activity in adult rat cardiomyocytes

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Differential effects of angiotensin AT1and AT2receptors on the expression, translation and function of the Na+-H+exchanger and Na+-HCO3−symporter in the rat heart after myocardial infarction

Abstract: Angiotensin II via its AT1 and AT2 receptors differentially controls transcriptional and translational regulation as well as the activity of NHE-1 and NBC-1 in the ischemic myocardium and contributes to the control of pH regulation in cardiac tissue.

Cited by 62 publications

References 49 publications

Enhanced activity of ventricular Na+-HCO3− cotransport in pressure overload hypertrophy

Enhanced activity of ventricular Na+-HCO3− cotransport in pressure overload hypertrophy

The Divergence, Actions, Roles, and Relatives of Sodium-Coupled Bicarbonate Transporters

The ERK pathway regulates Na+-HCO 3 − cotransport activity in adult rat cardiomyocytes

Contact Info

Product

Resources

About

Enhanced activity of ventricular Na⁺-HCO₃⁻ cotransport in pressure overload hypertrophy

Enhanced activity of ventricular Na⁺-HCO₃⁻ cotransport in pressure overload hypertrophy

The ERK pathway regulates Na⁺-HCO 3 − cotransport activity in adult rat cardiomyocytes