Vascular α1C and β3 subunits of L‐type calcium channels are coordinately upregulated in the mesenteric arteries of hypertensive C57BL6 mice

Abstract

Depolarization of vascular smooth muscle cells (VSMCs) opens L‐type calcium (CaL) channels to elicit Ca2+‐dependent contraction. CaL channels consist of pore‐forming α1C and one of four β subunits (β1‐4) that promote α1C expression. β3 is regarded as the major subunit in large arteries, but its functional role in resistance arteries is unclear. We hypothesized that α1C 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 CaL channel agonist FPL64176 (n=5), and CaL channel current density was increased 1.9‐fold in the mesenteric VSMCs (n=23). Western blots revealed a dual upregulation of α1C and β3 in MA from AHT mice and a marked increase in α1C and β3 immunofluorescence at the membrane of VSMCs. Collectively, our study suggests that: i) CaL channels are primary contributors to hypertension in the AHT mouse, and ii) the α1C/β3 complexes may be the molecular pathways for anomalous Ca2+ influx and vascular tone. Supported by R01 HL064806‐07 (NJR)