H+ Exchanger (h+ + exchanger)

Distribution by Scientific Domains


Selected Abstracts


Remote myocardium gene expression after 30 and 120 min of ischaemia in the rat

EXPERIMENTAL PHYSIOLOGY, Issue 2 2006
Miguel S. Guerra
The aim of the present study was to investigate how early the onset of ischaemia-induced changes in gene expression is in remote myocardium, and whether these changes would be different for left and right ventricles. Wistar rats (n= 27) were randomly assigned to left coronary artery (LCA) ligation for 30 or 120 min and sham groups. Evans Blue infusion revealed antero-apical left ventricle (LV) and left intraventricular (IV) septal ischaemia (35.5 ± 0.6% of LV mass). LCA ligation induced transient LV systolic dysfunction and sustained biventricular slowing of relaxation. Regarding mRNA levels, type B natriuretic peptide (BNP) was upregulated in the LV at 30 (+370 ± 191%) and 120 min (+221 ± 112%), whilst in the right ventricle (RV) this was only significant at 120 min (+128 ± 39%). Hipoxia-inducible factor 1, and interleukin 6 overexpression positively correlated with BNP. Inducible NO synthase upregulation was present in both ventricles at 120 min (LV, +327 ± 195%; RV, +311 ± 122%), but only in the RV at 30 min (+256 ± 88%). Insulin-like growth factor 1 increased in both ventricles at 30 (RV, +59 ± 18%; LV, +567 ± 192%) and 120 min (RV, +69 ± 33%; LV, +120 ± 24%). Prepro-endothelin-1 was upregulated in the RV at 120 min (+77 ± 25%). Ca2+ -handling proteins were selectively changed in the LV at 120 min (sarcoplasmic reticulum Ca2+ ATPase, 53 ± 7%; phospholamban, +31 ± 4%; Na+,Ca2+ exchanger, 31 ± 6%), while Na+,H+ exchanger was altered only in the RV (,79 ± 5%, 30 min; +155 ± 70%, 120 min). Tumour necrosis factor-, and angiotensin converting enzyme were not significantly altered. A very rapid modulation of remote myocardium gene expression takes place during myocardial ischaemia, involving not only the LV but also the RV. These changes are different in the two ventricles and in the same direction as those observed in heart failure. [source]


Relative contribution of V-H+ATPase and NA+/H+ exchanger to bicarbonate reabsorption in proximal convoluted tubules of old rats

AGING CELL, Issue 5 2006
Mariana Fiori
Summary With aging, the kidney develops a progressive deterioration of several structures and functions. Proximal tubular acidification is impaired in old rats with a decrease in the activity of brush border Na+/H+ exchange and a fall of H-ion flux measured with micropuncture experiments. In the present work we evaluate the contribution of 5-N-ethyl-n-isopropyl amiloride- (EIPA) and bafilomycin-sensitive bicarbonate flux () in proximal convoluted tubules of young and aged rats. We performed micropuncture experiments inhibiting the Na+/H+ exchanger with EIPA (10,4 M) and the V-H+ATPase with bafilomycin (10,6 M). We used antibodies against the NHE3 isoform of the Na+/H+ exchanger and the subunit E of the V-H+ATPase for detecting by Western blot the abundance of these proteins in brush border membrane vesicles from proximal convoluted tubules of young and old rats. The abundance of NHE3 and the V-H+ATPase was similar in 18-month-old and 3-month-old rats. The bicarbonate flux in old rats was 30% lower than in young rats. EIPA reduced by 60% and bafilomycin by 30% in young rats; in contrast, EIPA reduced by ,40% and bafilomycin by ,50% in old rats. The inhibited by bafilomycin was the same in young and old rats: 0.62 nmol · cm,2· s,1 and 0.71 nmol · cm,2· s,1, respectively. However, the EIPA-sensitive fraction was larger in young than in old rats: 1.26 nmol · cm,2· s,1 vs. 0.85 nmol · cm,2· s,1, respectively. These results suggest that the component more affected in bicarbonate reabsorption of proximal convoluted tubules from aged rats is the Na+ -H+ exchanger, probably a NHE isoform different from NHE3. [source]


Na+ -H+ exchanger 3 (NHE3) is present in lipid rafts in the rabbit ileal brush border: a role for rafts in trafficking and rapid stimulation of NHE3

THE JOURNAL OF PHYSIOLOGY, Issue 2 2001
Xuhang Li
1Rabbit ileal Na+ -absorbing cell Na+ -H+ exchanger 3 (NHE3) was shown to exist in three pools in the brush border (BB), including a population in lipid rafts. Approximately 50 % of BB NHE3 was associated with Triton X-100-soluble fractions and the other ,50 % with Triton X-100-insoluble fractions; ,33 % of the detergent-insoluble NHE3 was present in cholesterol-enriched lipid microdomains (rafts). 2The raft pool of NHE3 was involved in the stimulation of BB NHE3 activity with epidermal growth factor (EGF). Both EGF and clonidine treatments were associated with a rapid increase in the total amount of BB NHE3. This EGF- and clonidine-induced increase of BB NHE3 was associated with an increase in the raft pool of NHE3 and to a smaller extent with an increase in the total detergent-insoluble fraction, but there was no change in the detergent-soluble pool. In agreement with the rapid increase in the amount of NHE3 in the BB, EGF also caused a rapid stimulation of BB Na+ -H+ exchange activity. 3Disrupting rafts by removal of cholesterol with methyl-,-cyclodextrin (M,CD) or destabilizing the actin cytoskeleton with cytochalasin D decreased the amount of NHE3 in early endosomes isolated by OptiPrep gradient fractionation. Specifically, NHE3 was shown to associate with endosomal vesicles immunoisolated by anti-EEA1 (early endosomal autoantigen 1) antibody-coated magnetic beads and the endosome-associated NHE3 was decreased by cytochalasin D and M,CD treatment. 4We conclude that: (i) a pool of ileal BB NHE3 exists in lipid rafts; (ii) EGF and clonidine increase the amount of BB NHE3; (iii) lipid rafts and to a lesser extent, the cytoskeleton, but not the detergent-soluble NHE3 pool, are involved in the EGF- and clonidine-induced acute increase in amount of BB NHE3; (iv) lipid rafts and the actin cytoskeleton play important roles in the basal endocytosis of BB NHE3. [source]


Effects of combined inhibition of the Na+,H+ exchanger and angiotensin-converting enzyme in rats with congestive heart failure after myocardial infarction

BRITISH JOURNAL OF PHARMACOLOGY, Issue 5 2005
Hartmut Ruetten
We investigated the single vs the combined long-term inhibition of Na+,H+ exchanger-1 (NHE-1) and ACE in rats with congestive heart failure induced by myocardial infarction (MI). Rats with MI were randomized to receive either placebo, cariporide (3000 p.p.m. via chow), ramipril (1 mg kg,1 day,1via drinking water) or their combination for 18 weeks starting on day 3 after surgery. Cardiac morphology and function was assessed by echocardiography and by means of a 2.0 F conductance catheter to determine left ventricular (LV) pressure volume relationships. MI for 18 weeks resulted in an increase in LV end-diastolic diameter (LVDed) in the placebo-treated group when compared to sham (placebo: 1.1±0.04 cm; sham: 0.86±0.01; P<0.05). Combined inhibition of NHE-1 and ACE, but not the monotherapies, significantly reduced LVDed (1.02±0.02 cm). Preload recruitable stroke work (PRSW), dp/dtmax (parameter of systolic function) and end-diastolic pressure volume relationship (EDPVR, diastolic function) were significantly impaired in placebo-treated MI group (PRSW: 39±7 mmHg; dp/dtmax: 5185±363 mmHg s,1; EDPVR: 0.042±0.001 mmHg ,l,1; all P<0.05). Cariporide treatment significantly improved PRSW (64±7 mmHg), dp/dtmax (8077±525 mmHg s,1) and EDPVR (0.026±0.014 mmHg ,l,1), and reduced cardiac hypertrophy in rats with MI. Combined inhibition of NHE-1 and ACE had even a more pronounced effect on PRSW (72±5 mmHg) and EDPVR (0.026±0.014 mmHg ,l,1), as well as cardiac hypertrophy that, however, did not reach statistical significance compared to cariporide treatment alone. The NHE-1 inhibitor cariporide significantly improved LV remodeling and function in rats with congestive heart failure induced by MI. The effect of cariporide was comparable or tended to be stronger (e.g. systolic function) compared to ramipril. Combined treatment with cariporide and ramipril tended to be more effective on LV remodeling in rats with heart failure than the single treatments. Thus, inhibition of the NHE-1 may be a promising novel therapeutic approach for the treatment of congestive heart failure. British Journal of Pharmacology (2005) 146, 723,731. doi:10.1038/sj.bjp.0706381 [source]