Deficiency of T-type Ca²⁺ channels Ca_v3.1 and Ca_v3.2 has no effect on angiotensin II-induced hypertension but differential effect on plasma aldosterone in mice.

T-type Ca²⁺ channel Ca_v3.1 promotes microvessel contraction ex vivo. It was hypothesized that in vivo, functional deletion of Ca_v3.1, but not Ca_v3.2, protects mice against angiotensin II (ANG II)-induced hypertension. Mean arterial blood pressure (MAP) and heart rate were measured continuously with chronically indwelling catheters during infusion of ANG II (30 ng·kg^-1·min^-1, 7 days) in wild-type (WT), Ca_v3.1^-/-, and Ca_v3.2^-/- mice. Plasma aldosterone and renin concentrations were measured by radioimmunoassays. In a separate series, WT mice were infused with ANG II (100 ng·kg^-1·min^-1) with and without the mineralocorticoid receptor blocker canrenoate. Ca_v3.1^-/- and Ca_v3.2^-/- mice exhibited no baseline difference in MAP compared with WT mice, but day-night variation was blunted in both Ca_v3.1 and Ca_v3.2^-/- mice. ANG II increased significantly MAP in WT, Ca_v3.1^-/-, and Ca_v3.2^-/- mice with no differences between genotypes. Heart rate was significantly lower in Ca_v3.1^-/- and Ca_v3.2^-/- mice compared with control mice. After ANG II infusion, plasma aldosterone concentration was significantly lower in Ca_v3.1^-/- compared with Ca_v3.2^-/- mice. In response to ANG II, fibrosis was observed in heart sections from both WT and Ca_v3.1^-/- mice and while cardiac atrial natriuretic peptide mRNA was similar, the brain natriuretic peptide mRNA increase was mitigated in Ca_v3.1^-/- mice ANG II at 100 ng/kg yielded elevated pressure and an increased heart weight-to-body weight ratio in WT mice. Cardiac hypertrophy, but not hypertension, was prevented by the mineralocorticoid receptor blocker canrenoate. In conclusion, T-type channels Ca_v3.1and Ca_v3.2 do not contribute to baseline blood pressure levels and ANG II-induced hypertension. Ca_v3.1, but not Ca_v3.2, contributes to aldosterone secretion. Aldosterone promotes cardiac hypertrophy during hypertension.

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