Membrane acid‐base transporters modulate artery structure

Abstract

Acid‐base transport and pH control modulate cell proliferation and migration with possible consequences for artery remodeling. Here, we used knockout mice for the Na+/H+‐exchanger NHE1 and Na+,HCO3−‐cotransporter NBCn1 to study their role in determining arterial structure. Measurements were performed using pH‐sensitive fluorophores, myography and stereological analyses. NHE1 mediated the Na+/H+‐exchange in mesenteric arteries, and knockout of NHE1 was associated with reduced media thickness and an equivalent inhibition of maximum active tension development. The reduced media thickness was due to a smaller smooth muscle cell volume and cross‐sectional area with no change in the number of smooth muscle cells per unit artery length. NBCn1 mediated the Na+,HCO3−‐cotransport in carotid arteries. Following partial carotid artery ligation, the inward remodeling (reduction in carotid artery diameter and increase in media area) in wild type mice was more than 50% attenuated in NBCn1 knockout mice. In conclusion, we show that the acid‐base transport proteins NBCn1 and NHE1 play an important role for determining artery structure. Supported by Danish Council for Independent Research and Danish Heart Foundation.