PMC

A, mean arterial blood pressure (MAP) was lower in NHE1 KO compared to WT mice. B, no difference in heart rate (HR) was seen between NHE1 KO and WT mice. Comparisons were made with Student's unpaired, two-tailed t test. *P < 0.05; NS: not significantly different vs. WT.

A, tension development to noradrenaline was reduced in arteries from NHE1 KO compared to WT mice (P < 0.05; n= 8–10). Experiments were performed in the presence of CO₂/HCO₃⁻. B, the VSMC Ca²⁺ response to noradrenaline was unaffected in arteries from NHE1 KO compared to WT mice (P= 0.72; n= 4–5). For comparisons, sigmoidal curve fits were performed and the derived log(EC₅₀) and maximum values compared by extra sum-of-squares F tests.

A, no difference was found in the EC Ca²⁺ response to acetylcholine between arteries from NHE1 KO and WT mice (n= 5) investigated in the presence or absence of CO₂/HCO₃⁻. B, average increases in Ca²⁺-dependent fluorescence calculated from panel A. Comparisons were made with repeated measures two-way ANOVA followed by Bonferroni's post hoc test. NS: not significantly different.

A, in the absence of CO₂/HCO₃⁻, the acidification upon Na⁺ removal was abolished in ECs of arteries from NHE1 KO mice (n= 5). B, in the absence of CO₂/HCO₃⁻, steady-state pH_i was reduced in ECs of arteries from NHE1 KO mice compared to WT mice (n= 5). In the presence of CO₂/HCO₃⁻, no difference in steady-state pH_i was seen between ECs from NHE1 KO and WT mice (n= 4). Comparisons were made with a two-way ANOVA followed by Bonferroni's post hoc test. **P < 0.01 vs. WT.

A, relaxation of arteries from WT mice (n= 5) to acetylcholine was unaffected by removal of CO₂/HCO₃⁻ in the presence (P= 0.72) and in the absence (P= 0.73) of 100 μm l-NAME. B, relaxation of arteries from NHE1 KO mice (n= 5) to acetylcholine was attenuated upon removal of CO₂/HCO₃⁻ (P < 0.001). After pretreatment with 100 μm l-NAME, no effect of removing CO₂/HCO₃⁻ was seen (P= 0.65). C, no significant difference (P= 0.96) in the relaxation to the NO donor SNAP was found between arteries from NHE1 KO and WT mice in the presence or absence of CO₂/HCO₃⁻. Sigmoidal curve fits were performed and the derived log(EC₅₀) and maximum values compared by extra sum-of-squares F tests.

A, concentration–response curves showing average tension development to noradrenaline with or without 100 μm l-NAME and 10 μm Y-27632 in arteries from WT and NHE1 KO mice (n= 4–9) in the absence of CO₂/HCO₃⁻. B, summary of the changes in noradrenaline sensitivity with respect to tension development in arteries from NHE1 KO and WT mice (n= 4–9) investigated in the absence of CO₂/HCO₃⁻. C, concentration–response curves showing the average VSMC Ca²⁺ response to noradrenaline in the presence of 100 μm l-NAME or the combination of l-NAME and 10 μm Y-27632 in arteries from NHE1 KO and WT mice (n= 5) in the absence of CO₂/HCO₃⁻. Sigmoidal curve fits were performed and the derived log(EC₅₀) and maximum values compared by extra sum-of-squares F tests. **P < 0.01; NS: not significantly different vs. WT.

A, in the absence of CO₂/HCO₃⁻, the Na⁺-dependent pH_i recovery was abolished in VSMCs of arteries from NHE1 KO mice (n= 5–7). Experiments were performed in the absence of CO₂/HCO₃⁻ except for the final part (as indicated). B, the Na⁺- and HCO₃⁻-dependent, amiloride-insensitive pH_i recovery was unaltered in VSMCs of arteries from NHE1 KO mice (n= 5–6). Experiments were performed in the presence of CO₂/HCO₃⁻. C, average net H⁺ extrusion from VSMCs measured at average pH_i values between 6.43 and 6.65. Na⁺/H⁺ exchange was abolished while Na⁺–HCO₃⁻ cotransport was unaffected in arteries from NHE1 KO mice. Comparisons were made with Student's two-tailed unpaired t test. D, in the absence of CO₂/HCO₃⁻, steady-state pH_i was lower in VSMCs of arteries from NHE1 KO than WT mice. In the presence of CO₂/HCO₃⁻, no significant difference in steady-state pH_i was seen between VSMCs of arteries from NHE1 KO and WT mice (n= 5–8). Comparisons were made with a two-way ANOVA followed by Bonferroni's post hoc test. ***P < 0.001; NS: not significantly different vs. WT.