{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T05:59:10Z","timestamp":1792648750704,"version":"4.5.0"},"reference-count":62,"publisher":"Wiley","issue":"21","license":[{"start":{"date-parts":[[2014,9,29]],"date-time":"2014-09-29T00:00:00Z","timestamp":1411948800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2014,11]]},"abstract":"<jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\"><jats:list-item><jats:p>We studied the effects of antihypertensive calcium channel blockers on Ca<jats:sub>V<\/jats:sub>1.2, the predominantly expressed L\u2010type calcium channel in the largest human lymphatic vessel, the thoracic duct.<\/jats:p><\/jats:list-item><jats:list-item><jats:p>Human lymphatic collecting vessels, both large and small, are highly\u2010sensitive<jats:italic>in vitro<\/jats:italic>to calcium channel blockers; exposure to these drugs inhibits endogenous lymphatic contractile activity and action potentials and diminishes noradrenaline\u2010induced phasic contractions.<\/jats:p><\/jats:list-item><jats:list-item><jats:p><jats:italic>In vivo<\/jats:italic>administration of calcium channel blocker nifedipine to healthy volunteers did not reduce lymphatic contractile activity despite all subjects achieving nifedipine plasma concentrations comparable with those observed to affect contractile function<jats:italic>in vitro<\/jats:italic>.<\/jats:p><\/jats:list-item><jats:list-item><jats:p>These results indicate that calcium channel blocker\u2010related oedema is unlikely to be exacerbated by an off\u2010target effect of the drugs diminishing lymphatic pumping and fluid removal.<\/jats:p><\/jats:list-item><\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>Calcium channel blockers (CCB) are widely prescribed anti\u2010hypertensive agents. The commonest side\u2010effect, peripheral oedema, is attributed to a larger arterial than venous dilatation causing increased fluid filtration. Whether CCB treatment is detrimental to human lymphatic vessel function and thereby exacerbates oedema formation is unknown. We observed that spontaneous lymphatic contractions in isolated human vessels (thoracic duct and mesenteric lymphatics) maintained under isometric conditions were inhibited by therapeutic concentrations (nanomolar) of the CCB nifedipine while higher than therapeutic concentrations of verapamil (micromolar) were necessary to inhibit activity. Nifedipine also inhibited spontaneous action potentials measured by sharp microelectrodes. Furthermore, noradrenaline did not elicit normal increases in lymphatic vessel tone when maximal constriction was reduced to 29.4\u00a0\u00b1\u00a04.9% of control in the presence of 20\u00a0nmol\u00a0l<jats:sup>\u22121<\/jats:sup>nifedipine. Transcripts for the L\u2010type calcium channel gene<jats:italic>CACNA1C<\/jats:italic>were consistently detected from human thoracic duct samples examined and the Ca<jats:sub>V<\/jats:sub>1.2 protein was localized by immunoreactivity to lymphatic smooth muscle cells. While human lymphatics<jats:italic>ex vivo<\/jats:italic>were highly sensitive to nifedipine, this was not apparent<jats:italic>in vivo<\/jats:italic>when nifedipine was compared to placebo in a randomized, double\u2010blinded clinical trial: conversely, lymphatic vessel contraction frequency was increased and refill time was faster despite all subjects achieving target nifedipine plasma concentrations. We conclude that human lymphatic vessels are highly sensitive to nifedipine<jats:italic>in vitro<\/jats:italic>but that care must be taken when extrapolating<jats:italic>in vitro<\/jats:italic>observations of lymphatic vessel function to the clinical situation, as similar changes in lymphatic function were not evident in our clinical trial comparing nifedipine treatment to placebo.<\/jats:p><\/jats:sec>","DOI":"10.1113\/jphysiol.2014.276683","type":"journal-article","created":{"date-parts":[[2014,8,29]],"date-time":"2014-08-29T10:10:25Z","timestamp":1409307025000},"page":"4697-4714","source":"Crossref","is-referenced-by-count":63,"title":["Human lymphatic vessel contractile activity is inhibited<i>in vitro<\/i>but not<i>in vivo<\/i>by the calcium channel blocker nifedipine"],"prefix":"10.1113","volume":"592","author":[{"given":"Niklas","family":"Telinius","sequence":"first","affiliation":[{"name":"Department of Biomedicine Aarhus University Aarhus Denmark"},{"name":"Department of 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