Regulation of Vascular Tone in Animals Overexpressing the Sarcolemmal Calcium Pump

Kai Schuh, Thomas Quaschning, Sebastian Knauer, Kai Hu, Serkan Koçak, Nicola Roethlein, Ludwig Neyses

    Research output: Contribution to journalArticlepeer-review


    The mechanisms governing vascular smooth muscle tone are incompletely understood. In particular, the role of the sarcolemmal calcium pump PMCA (plasma membrane calmodulin-dependent calcium ATPase), which extrudes Ca 2+ from the cytosol, and its importance compared with the sodium/calcium exchanger remain speculative. To test whether the PMCA is a regulator of vascular tone, we generated transgenic mice overexpressing the human PMCA4b under control of the arterial smooth muscle-specific SM22α promoter. This resulted in an elevated systolic blood pressure compared with littermate controls. In PMCA-overexpressing mice, endothelium-dependent relaxation of norepinephrine-preconstricted aortic rings to acetylcholine did not differ from wild type controls (76 ± 8% versus 79 ± 8% of maximum relaxation; n = 12, n.s.). De-endothelialized aortas of transgenic mice exhibited stronger maximum contraction to KCl (100 mmol/liter) compared with controls (86 ± 6% versus 68 ± 7% of reference KCl contraction at the beginning of the experiment; p <0.05). Preincubation of de-endothelialized vessels with the nitric oxide synthase (NOS) inhibitor L-NAME (L-N(G)-nitroarginine methyl ester) (10-5 mol/liter) resulted in a stronger contraction to KCl (p
    Original languageEnglish
    Pages (from-to)41246-41252
    Number of pages6
    JournalJournal of Biological Chemistry
    Issue number42
    Publication statusPublished - 17 Oct 2003


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