ISSN:
1432-1912
Keywords:
Cromakalim
;
Minoxidil sulphate
;
K+ channel opener
;
Glibenclamide 42K+/86Rb+ efflux
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Summary The effects of the K+ channel opening drugs minoxidil sulphate and cromakalim, on 42K+ and 86Rb+ efflux and on vasorelaxation in rat isolated aorta, were compared. In rat aortic rings precontracted with noradrenaline (100 nmol/l), minoxidil sulphate and cromakalim concentration-dependently inhibited induced tension by up to 90%, with pD2 values of 7.35±0.1 and 7.17±0.1, respectively. Glibenclamide (300 nmol/l), produced 2200- and 19-fold rightward shifts in the concentration-relaxation curves to minoxidil sulphate and cromakalim, respectively, without an effect on the maximum relaxation. Both minoxidil sulphate and cromakalim increased the efflux of 42K+ and 86Rb+ from aorta in a concentration-dependent manner, with midpoints in the µmol/l range; the maximum efflux induced by minoxidil sulphate being approximately one tenth of that induced by cromakalim. The ratio of stimulated 86Rb+/42K+ efflux increased from 0.22 to 0.48 with increasing cromakalim concentrations, but was approximately constant (≈0.39) when the minoxidil sulphate concentration was varied. In the presence of minoxidil sulphate, the effects of cromakalim on 42K+ and 86Rb+ efflux were inhibited in a concentration-dependent manner, by up to 60%. In the continuing presence of cromakalim (300 nmol/l), minoxidil sulphate (10 µmol/l)-induced increases in 42K+ and 86Rb+ efflux were inhibited by 45%, whereas conditioning with cromakalim (1 µmol/l) inhibited the 86Rb+ efflux stimulated by additional superfusion of cromakalim (1 µmol/l) by 85%. Glibenclamide inhibited minoxidil sulphate (10 µmol/l)- and cromakalim (1 µmol/l)-induced increases in 42K+ and 86Rb+ efflux in a concentration-dependent manner with IC50 values of approximately 80 nmol/l. In conclusion, the efflux data suggest that considerable overlap exists between the channels opened by minoxidil sulphate and those opened by cromakalim in rat aorta. Minoxidil sulphate has a weak efficacy as a K+ channel opener, and may act to open a homogeneous population of K+ channels. In contrast, the actions of cromakalim (≥1 µmol/l) are associated with large increases in tracer efflux, which are probably mediated via a heterogeneous population of K+ channels. However, only a small proprtion of this induced efflux appears to be required for relaxation. The differential inhibition by glibenclamide of the vasorelaxant effects of minoxidil sulphate and cromakalim may result from (a) the partial agonist properties of minoxidil sulphate in opening K+ channels and/or (b) additional mechanisms of vasorelaxation, which differ in their sensitivity to glibenclamide.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00183011
