Vascular reactivity to nifedipine and Ca(2+) in vitro: the role of preactivation, wall tension and geometry.
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.
Tankó
L B
LB
Department of Pharmacology, Aarhus University, The Bartholin Building 240, DK-8000, Aarhus, Denmark. ltanko@farm.aau.dk
Simonsen
U
U
Frøbert
O
O
Gregersen
H
H
Bagger
J P
JP
Mikkelsen
E O
EO
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
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D009543:Nifedipine; D011188:Potassium; D002118:Calcium