Vascular α 1C and β3 subunits of L‐type calcium channels are coordinately upregulated in the mesenteric arteries of hypertensive C57BL6 mice

Depolarization of vascular smooth muscle cells (VSMCs) opens L‐type calcium (Ca L ) channels to elicit Ca 2+ ‐dependent contraction. Ca L channels consist of pore‐forming α 1C and one of four β subunits (β1‐4) that promote α 1C expression. β3 is regarded as the major subunit in large arteries, but its functional role in resistance arteries is unclear. We hypothesized that α 1C and β3 are coordinately upregulated in hypertension. We infused C57BL6 mice with Angiotensin II (Ang II, 2 ng/g/min, 2 weeks) using osmotic minipumps to establish hypertension. Systolic blood pressures (SBPs) were 170 ± 10 mm Hg in Ang II hypertensive (AHT) mice compared to 114 ± 3 mm Hg in saline infused control mice. Nifedipine (5 mg/kg, i.p.) restored SBP to normal levels in AHT but only mildly lowered SBP in control mice. Isolated mesenteric arteries (MA) from AHT mice showed a 5.1‐fold higher contractile sensitivity to the Ca L channel agonist FPL64176 (n=5), and Ca L channel current density was increased 1.9‐fold in the mesenteric VSMCs (n=23). Western blots revealed a dual upregulation of α 1C and β3 in MA from AHT mice and a marked increase in α 1C and β3 immunofluorescence at the membrane of VSMCs. Collectively, our study suggests that: i) Ca L channels are primary contributors to hypertension in the AHT mouse, and ii) the α 1C /β3 complexes may be the molecular pathways for anomalous Ca 2+ influx and vascular tone. Supported by R01 HL064806‐07 (NJR)