Differential vasorelaxant effects of levcromakalim and P1060 in the isolated KCl- and RbCl-precontracted human saphenous vein: possible involvement of intracellular Ca2+ stores.
The influence of rubidium-substituted physiological salt solution (Rb-PSS) on the relaxant effects of K+ channel openers was investigated in the human saphenous vein. In tissues precontracted with 20 mM KCl (in K-PSS) levcromakalim and P1060 produced complete, sustained relaxations. However, in Rb-PSS (containing 20 mM RbCl) these effects were inhibited and, although complete relaxations still occurred, were transient. When caffeine was applied at the beginning of this fade of levcromakalim-induced relaxation in Rb-PSS its contractile effect was potentiated. Similarly, the contraction to noradrenaline was potentiated when applied at the beginning of this fade of levcromakalim-induced relaxation, whereas this response was attenuated in control tissues bathed in 20 mM KCl (in K-PSS). Our results show that the relaxant effects of K+ channel openers in human saphenous vein are inhibited in Rb-PSS, in agreement with previous studies in animal tissue, and suggest that an increased Ca2+ uptake into intracellular stores may be contributory to vasorelaxation.
Criddle
D N
DN
Departamento de Farmacologia, Universidade do Estado do Rio de Janeiro, Brazil.
Jazbik
W
W
de Moura
R S
RS
D001578:Benzopyrans / Q000494:pharmacology*; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000502:physiology*; D002712:Chlorides / Q000494:pharmacology; D019806:Cromakalim; D006146:Guanidines / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D009543:Nifedipine / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects*; D011189:Potassium Chloride / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology*; D012413:Rubidium / Q000494:pharmacology; D012501:Saphenous Vein / Q000187:drug effects / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology*
D001578:Benzopyrans; D002712:Chlorides; D006146:Guanidines; D015221:Potassium Channels; D011758:Pyrroles; D014665:Vasodilator Agents; D019806:Cromakalim; D002110:Caffeine; C058754:N'-cyano-N-(3-pyridyl)-N''-(t-butyl)guanidine; D011189:Potassium Chloride; D009543:Nifedipine; D012413:Rubidium; C032710:rubidium chloride; D002118:Calcium; D009638:Norepinephrine