T-type Ca(2+) channels facilitate NO-formation, vasodilatation and NO-mediated modulation of blood pressure

Per Svenningsen, Kenneth Andersen, Anne D Thuesen, Hee-Sup Shin, Paul M Vanhoutte, Ole Skøtt, Boye L Jensen, Caryl Hill, Pernille B L Hansen

Research output: Contribution to journalJournal article

Abstract

Voltage-gated calcium channels are involved in the vascular excitation-contraction mechanism and regulation of arterial blood pressure. It was hypothesized that T-type channels promote formation of nitric oxide from the endothelium. The present experiments determine the involvement of T-type channels in depolarization-dependent dilatation of mesenteric arteries and blood pressure regulation in Cav3.1 knock-out mice. Nitric oxide-dependent vasodilatation following depolarization-mediated vasoconstriction was reduced significantly in mesenteric arteries from Cav3.1(-/-) compared to wild type mice. Four days of systemic infusion of a nitric oxide (NO)-synthase-inhibitor to conscious wild type elicited a significant increase in mean arterial blood pressure that was absent in Cav3.1(-/-) mice. Immunoprecipitation and immunofluorescence labeling showed co-localization of Cav3.1 and endothelial nitric oxide synthase (eNOS) in arteries from wild type mice. Nitric oxide release measured as DAF fluorescence and cGMP levels were significantly lower in depolarized Cav3.1(-/-) compared to wild type arteries. In summary, the absence of T-type Cav3.1 channels attenuates NO-dependent dilatation in mesenteric arteries in vitro, as well as the hypertension after L-NAME infusion in vivo. Furthermore, Cav3.1 channels cluster with eNOS and promote formation of nitric oxide by the endothelium. The present findings suggest that this mechanism is important for the systemic impact of NO on peripheral resistance.
Original languageEnglish
JournalPflügers Archiv - European Journal of Physiology
Volume466
Issue number12
Pages (from-to)2205-2214
ISSN0031-6768
DOIs
Publication statusPublished - 2014

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