title: Vascular reactivity to nifedipine and Ca(2+) in vitro: the role of preactivation, wall tension and geometry.
abstract: The purpose of the study was to investigate the influence of preactivation, wall tension and geometry on the reactivity of porcine coronary arteries to nifedipine and extracellular Ca(2+) in vitro. Porcine large coronary arteries were mounted as ring and cylindrical preparations and studied by wire- and balloon-based techniques. The sensitivity and maximal responses to nifedipine were more pronounced in 25 mM K(+) compared to 10 microM prostaglandin F(2alpha)-contracted preparations. Vascular sensitivity to nifedipine and Ca(2+) was enhanced under isometric compared to isobaric conditions. Under isometric conditions in the presence of 25 mM K(+), coronary rings were more sensitive to nifedipine, but less sensitive to Ca(2+) compared to cylindrical segments. In cylindrical segments, circumferential and axial tension increases augmented the extracellular Ca(2+)-dependent spontaneous resting tone and the sensitivity to extracellular Ca(2+). Coronary rings showed no resting tone at various resting tensions. These results suggest that preactivation, wall tension and vessel geometry are important determinants of Ca(2+)-influxes via nifedipine-sensitive voltage-gated Ca(2+) channels. Furthermore, axial wall tension appears to be a modulator of nifedipine-insensitive transmembrane Ca(2+)-influx that may play a role for the tone and reactivity in large coronary arteries.
authors.affiliation: Department of Pharmacology, Aarhus University, The Bartholin Building 240, DK-8000, Aarhus, Denmark. ltanko@farm.aau.dk
authors.forename: L B
authors.initials: LB
authors.lastname: Tankó
authors.forename: U
authors.initials: U
authors.lastname: Simonsen
authors.forename: O
authors.initials: O
authors.lastname: Frøbert
authors.forename: H
authors.initials: H
authors.lastname: Gregersen
authors.forename: J P
authors.initials: JP
authors.lastname: Bagger
authors.forename: E O
authors.initials: EO
authors.lastname: Mikkelsen
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000502:physiology; D003331:Coronary Vessels / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000502:physiology; D066298:In Vitro Techniques; D009543:Nifedipine / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology; D013552:Swine; D014661:Vasoconstriction / Q000187:drug effects
chemical_list: D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D009543:Nifedipine; D011188:Potassium; D002118:Calcium