Ca2+-dependence of vasoconstriction mediated by alpha1A-adrenoceptors in perfused rat hindlimb: a pharmacological approach.
We investigated the source of Ca2+ for the vasoconstriction mediated by alpha1a-adrenoceptors in perfused rat hindlimb in functional studies. The noradrenaline (NA)-induced maximum response was decreased by 92% following perfusion with Ca2+-free medium. Depletion of intracellular Ca2+-stores with repeatedly application of caffeine and NA in Ca2+-free medium resulted in complete abolishment of NA-response. Nifedipine concentration-dependently inhibited NA-contraction with a maximum inhibition of 65%. The residual nifedipine-insensitive response was further inhibited by Cd2+. Following depletion of Ca2+ stores with cyclopiazonic acid in Ca2+ free medium for 30 min, the NA-response obtained by re-admission of Ca2+ was decreased by 80%. However, re-introduction of Ca2+ to NA-treated tissues in Ca2+-free medium without prior treatment with cyclopiazonic acid normalizes the NA-response. These results suggest that the NA-contraction in this preparation is mediated largely via an influx of extracellular Ca2+, of which the majority utilizes L-type calcium channels. Only a small portion of the contractile response to NA is derived from intracellular stores, which probably also play a modulatory role on Ca2+ influx.
Institute of Vascular Medicine, The Third Hospital, Beijing Medical University, China.
W Z
WZ
Zhu
C Y
CY
Kwan
C
C
Han
D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism; D006614:Hindlimb / Q000098:blood supply / Q000187:drug effects; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D009543:Nifedipine / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
D015220:Calcium Channels; D018340:Receptors, Adrenergic, alpha-1; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D002110:Caffeine; D009543:Nifedipine; D002118:Calcium; D009638:Norepinephrine