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

<jats:p> T-type Ca<jats:sup>2+</jats:sup> channel Ca<jats:sub>v</jats:sub>3.1 promotes microvessel contraction ex vivo. It was hypothesized that in vivo, functional deletion of Ca<jats:sub>v</jats:sub>3.1, but not Ca<jats:sub>v</jats:sub>3.2, 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<jats:sup>−1</jats:sup>·min<jats:sup>−1</jats:sup>, 7 days) in wild-type (WT), Ca<jats:sub>v</jats:sub>3.1<jats:sup>−/−</jats:sup>, and Ca<jats:sub>v</jats:sub>3.2<jats:sup>−/−</jats:sup> mice. Plasma aldosterone and renin concentrations were measured by radioimmunoassays. In a separate series, WT mice were infused with ANG II (100 ng·kg<jats:sup>−1</jats:sup>·min<jats:sup>−1</jats:sup>) with and without the mineralocorticoid receptor blocker canrenoate. Ca<jats:sub>v</jats:sub>3.1<jats:sup>−/−</jats:sup> and Ca<jats:sub>v</jats:sub>3.2<jats:sup>−/−</jats:sup> mice exhibited no baseline difference in MAP compared with WT mice, but day-night variation was blunted in both Ca<jats:sub>v</jats:sub>3.1 and Ca<jats:sub>v</jats:sub>3.2<jats:sup>−/−</jats:sup> mice. ANG II increased significantly MAP in WT, Ca<jats:sub>v</jats:sub>3.1<jats:sup>−/−</jats:sup>, and Ca<jats:sub>v</jats:sub>3.2<jats:sup>−/−</jats:sup> mice with no differences between genotypes. Heart rate was significantly lower in Ca<jats:sub>v</jats:sub>3.1<jats:sup>−/−</jats:sup> and Ca<jats:sub>v</jats:sub>3.2<jats:sup>−/−</jats:sup> mice compared with control mice. After ANG II infusion, plasma aldosterone concentration was significantly lower in Ca<jats:sub>v</jats:sub>3.1<jats:sup>−/−</jats:sup> compared with Ca<jats:sub>v</jats:sub>3.2<jats:sup>−/−</jats:sup> mice. In response to ANG II, fibrosis was observed in heart sections from both WT and Ca<jats:sub>v</jats:sub>3.1<jats:sup>−/−</jats:sup> mice and while cardiac atrial natriuretic peptide mRNA was similar, the brain natriuretic peptide mRNA increase was mitigated in Ca<jats:sub>v</jats:sub>3.1<jats:sup>−/−</jats:sup> 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<jats:sub>v</jats:sub>3.1and Ca<jats:sub>v</jats:sub>3.2 do not contribute to baseline blood pressure levels and ANG II-induced hypertension. Ca<jats:sub>v</jats:sub>3.1, but not Ca<jats:sub>v</jats:sub>3.2, contributes to aldosterone secretion. Aldosterone promotes cardiac hypertrophy during hypertension. </jats:p>