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Acta Physiologica 2011; Volume 202, Supplement 685
Scandinavian Physiological Society's Annual Meeting
8/12/2011-8/14/2011
Bergen, Norway
MEMBRANE ACID-BASE TRANSPORT IN ENDOTHELIAL CELLS: MOLECULAR MECHANISMS AND IMPLICATIONS FOR ARTERY FUNCTION
Abstract number: 5.2.6
BOEDTKJER1 E, PRAETORIUS1 J, MATCHKOV V(1), STANKEVICIUS1 E, DAMKIER1 H, FUCHTBAUER1 E, AALKJAER1 C
1Department of Physiology and Biophysics, Aarhus University. Ole Worms Alle 6, building 1180, DK8000 Aarhus C, Denmark; Email: [email protected]
Aims:
We studied membrane acid-base transport in endothelial cells of mouse resistance arteries. Particularly, we investigated the role of Na+,HCO3 --cotransporter NBCn1 and Na+/H+exchanger NHE1 for resistance artery function and blood pressure regulation.
Methods:
The function of isolated arteries was assessed using myography combined with fluorescence microscopy and NO-sensitive electrodes. Protein expression was investigated using Western blot analyses, immunofluorescence imaging and immunogold electron microscopy. Blood pressure effects were studied using radiotelemetry or tail-cuff measurements.
Results:
Knockout of NBCn1 acidified mesenteric artery endothelial cells and abolished all endothelial Na+,HCO3 -cotransport. Arteries from NBCn1 knockout mice displayed reduced NO-mediated relaxations and a smaller increase in intraluminal [NO] upon stimulation with acetylcholine. The reduced relaxation persisted after superoxide-scavenging. No change in endothelial NO-synthase expression was seen. NBCn1 knockout mice were mildly hypertensive (~9 mmHg) at rest and showed an attenuated blood pressure increase to NO-synthase inhibition. Knockout of NHE1 abolished all endothelial Na+/H+-exchange and caused endothelial acidification in the absence of CO2/HCO3 - . Under these conditions, arteries from NHE1 knockout mice showed reduced NO-mediated vasorelaxation. Dilation to the NO-donor S-nitroso-N-acetylpenicillamine and the acetylcholine-induced endothelial Ca2+-increase were unaffected by NBCn1 and NHE1 knockout.
Conclusion:
We show that endothelial intracellular pH regulation depends on membrane acid-base transport mediated by NBCn1 and NHE1. Endothelial acidification inhibits NO-mediated vasorelaxation of resistance arteries with implications for blood pressure regulation.
To cite this abstract, please use the following information:
Acta Physiologica 2011; Volume 202, Supplement 685 :5.2.6