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.