Abstract |
T-type Ca2+ channel Cav3.1 promotes microvessel contraction ex vivo. It was hypothesized that in vivo, functional deletion of Cav3.1, but not Cav3.2, 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), Cav3.1-/-, and Cav3.2-/- 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. Cav3.1-/- and Cav3.2-/- mice exhibited no baseline difference in MAP compared with WT mice, but day-night variation was blunted in both Cav3.1 and Cav3.2-/- mice. ANG II increased significantly MAP in WT, Cav3.1-/-, and Cav3.2-/- mice with no differences between genotypes. Heart rate was significantly lower in Cav3.1-/- and Cav3.2-/- mice compared with control mice. After ANG II infusion, plasma aldosterone concentration was significantly lower in Cav3.1-/- compared with Cav3.2-/- mice. In response to ANG II, fibrosis was observed in heart sections from both WT and Cav3.1-/- mice and while cardiac atrial natriuretic peptide mRNA was similar, the brain natriuretic peptide mRNA increase was mitigated in Cav3.1-/- 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 Cav3.1and Cav3.2 do not contribute to baseline blood pressure levels and ANG II-induced hypertension. Cav3.1, but not Cav3.2, contributes to aldosterone secretion. Aldosterone promotes cardiac hypertrophy during hypertension.
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Authors | Anne D Thuesen, Stine H Finsen, Louise L Rasmussen, Ditte C Andersen, Boye L Jensen, Pernille B L Hansen |
Journal | American journal of physiology. Renal physiology
(Am J Physiol Renal Physiol)
Vol. 317
Issue 2
Pg. F254-F263
(08 01 2019)
ISSN: 1522-1466 [Electronic] United States |
PMID | 31042060
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Biomarkers
- Cacna1g protein, mouse
- Cacna1h protein, mouse
- Calcium Channels, T-Type
- Mineralocorticoid Receptor Antagonists
- Receptors, Angiotensin
- Angiotensin II
- Aldosterone
- Canrenoic Acid
- Cytochrome P-450 CYP11B2
- Renin
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Topics |
- Adrenal Glands
(enzymology)
- Aldosterone
(blood)
- Angiotensin II
- Animals
- Arterial Pressure
(drug effects)
- Biomarkers
(blood)
- Calcium Channels, T-Type
(deficiency, genetics)
- Canrenoic Acid
(pharmacology)
- Cardiomegaly
(blood, genetics, pathology)
- Cytochrome P-450 CYP11B2
(metabolism)
- Disease Models, Animal
- Female
- Fibrosis
- Hypertension
(blood, genetics, physiopathology, prevention & control)
- Male
- Mice, Inbred C57BL
- Mice, Knockout
- Mineralocorticoid Receptor Antagonists
(pharmacology)
- Myocardium
(metabolism, pathology)
- Receptors, Angiotensin
(metabolism)
- Renin
(blood)
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