Na + ‐K + ATPase and Ca 2+ Clearance Proteins: A Coordinated Unit in Smooth Muscle?

Na + −K + ATPase (NKA) has been hypothesized to be involved in hypertension in part by influencing Ca 2+ handling via coupling to Na + −Ca 2+ exchanger (NCX). The specific contribution of smooth muscle NKA to systolic blood pressure is not known with certainty. We previously developed mice that expressed a transgene for the NKA α2‐isoform using the smooth muscle SMP8 promoter (α2 sm+ mice). These mice had a 2–7‐fold increase in α2‐isoform protein, and decreased systolic blood pressure and relaxation half‐times of aortic force. Surprisingly, α2 sm+ mice also had a similar increase in the NKA α1‐isoform, not contained in the transgene. To elucidate mechanisms for the decreased systolic blood pressure, we measured NCX, sarcoplasmic reticulum Ca 2+ ATPase (SERCA), and plasma membrane Ca 2+ ATPase (PMCA) protein levels. There was a 2–5‐fold increase in SERCA, NCX, and PMCA in aortic and antral smooth muscle from α2 sm+ mice compared to WT mice. In contrast, actin and myosin light chain were not changed in α2 sm+ aorta, suggesting no vascular remodeling. Our data suggest that NKA may be involved in a larger, regulated Ca 2+ clearing unit, consisting of at least NKA, NCX, SERCA, and PMCA, which may be important in coordinating control of [Ca 2+ ] i . Supported by HL66044, HL61974.