Blood pressure and vascular reactivity in ACTH‐treated mice with ouabain‐resistant α2 Na‐K‐ATPase

We have shown that alterations in the ouabain‐binding characteristics of the α1 and α2 subunits of the Na‐K‐ATPase (NKA) can influence cardiovascular function in vivo . Notably, we have reported that ACTH‐induced hypertension is prevented in mice expressing a mutant, ouabain‐resistant α2NKA isoform. To explore this ACTH‐resistance, we evaluated regional vascular resistance in ouabain‐resistant α2NKA (α2R) and ouabain‐sensitive α2NKA mice (wild type: WT). Mice were treated for 5–6 days with ACTH, or sham treated, then prepared for blood pressure and flow measurements. In untreated mice, there were no differences in blood pressure, renal and mesenteric blood flow or vascular resistance under baseline conditions, and sensitivity to phenylephrine (PE) was comparable between the two groups. In ACTH‐treated mice, resting blood pressure was lower in α2R than in WT, confirming that hypertension is prevented in these mutants. Following ACTH‐treatment, renal and mesenteric blood flow decreased significantly in α2R, but not in WT mice. Calculations of vascular resistance confirmed that resting vascular resistance was paradoxically elevated in the hypertension‐resistant α2R mice. PE‐responsiveness was also enhanced in the ACTH‐treated α2R mice compared to untreated, whereas PE‐responsiveness was not altered by ACTH in WT. These data suggest that the anti‐hypertensive phenotype of ouabain‐resistant α2NKA mice occurs in spite of increased reactivity in these vascular beds.