Upregulation of vascular L‐type calcium channels during hypertension is blunted in the absence of accessory β3 subunits

Depolarization of vascular smooth muscle cells (VSMCs) opens L‐type Ca 2+ (Ca L ) channels to elicit vasoconstriction. Ca L channels in large arteries appear to be composed of a pore‐forming α 1C subunit and an accessory β2 or β3 subunit that promotes channel expression. Our goal was to define the contribution of β subunits to Ca L channel expression in mouse mesenteric arteries (MA). Only β3 transcript (not β2) was detected by RT‐PCR in mesenteric VSMCs, and expression of the β3 protein was confirmed by Western blot. Subsequently, we hypothesized that the upregulation of Ca L channels in MA and development of hypertension would be less profound in β3KO mice compared to wild‐type (WT) mice. Basal levels of systolic blood pressure (SBP) were similar between WT and β3KO mice, but MA from β3KO mice expressed 30±8% less α 1C protein compared to WT mice (n=5). The α 1C and β3 proteins coordinately upregulated in MA of WT mice infused with angiotensin II (Ang II, 2 ng/gm/min; 2 weeks) to induce hypertension (SBP = 180±5 mmHg). In contrast, the upregulation of α 1C in response to Ang II was blunted in MA of β3KO mice and these mice had lower SBP (152±5 mmHg). These findings suggest that: i) β3 may be the sole β subunit in mouse MA, ii) resting SBP does not rely on the full expression of α 1C and β3; and iii) the β3 subunit is involved in the upregulation of vascular Ca L channels during hypertension. Funding AHA 09PRE2250224 (SVK) and NIH R01 HL064806 ‐ 10 (NJR).