The action of diazoxide and minoxidil sulphate on rat blood vessels: a comparison with cromakalim.
1. The actions of diazoxide and minoxidil sulphate have been compared with those of cromakalim in rat aorta and portal vein. 2. Diazoxide and minoxidil sulphate hyperpolarized the rat portal vein in a similar manner to cromakalim. 3. Cromakalim, diazoxide and minoxidil sulphate increased 42K and 86Rb efflux from rat portal vein, although minoxidil sulphate had only a small effect on 86Rb efflux. 4. Cromakalim, diazoxide and minoxidil sulphate increased 42K efflux from rat aorta but only cromakalim and diazoxide increased 86Rb efflux from this tissue. 5. Glibenclamide inhibited the relaxant actions of cromakalim, diazoxide and minoxidil sulphate on rat aorta and the increase in 42K efflux produced by these agents in this tissue. 6. Diazoxide relaxed an 80 mM KCl-induced contraction of rat aorta, whilst cromakalim and minoxidil sulphate were without effect. 7. Cromakalim, diazoxide and minoxidil sulphate had no effect on cyclic AMP or cyclic GMP concentrations in rat aorta. 8. It is concluded that diazoxide and minoxidil sulphate like cromakalim exhibit K+ channel opening properties in vascular smooth muscle. Diazoxide exerts an additional inhibitory action not related to the production of cyclic AMP or cyclic GMP. The action of minoxidil sulphate may be primarily located at a K+ channel which is relatively impermeable to 86Rb.
Newgreen
D T
DT
Department of Physiological Sciences, University of Manchester.
Bray
K M
KM
McHarg
A D
AD
Weston
A H
AH
Duty
S
S
Brown
B S
BS
Kay
P B
PB
Edwards
G
G
Longmore
J
J
Southerton
J S
JS
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001013:Aorta, Thoracic / Q000187:drug effects; D001578:Benzopyrans / Q000494:pharmacology*; D019806:Cromakalim; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D003981:Diazoxide / Q000494:pharmacology*; D005905:Glyburide / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008839:Microelectrodes; D008914:Minoxidil / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D011169:Portal Vein / Q000502:physiology; D015221:Potassium Channels / Q000187:drug effects; D011197:Potassium Radioisotopes; D011758:Pyrroles / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D012414:Rubidium Radioisotopes
D000959:Antihypertensive Agents; D001578:Benzopyrans; D015221:Potassium Channels; D011197:Potassium Radioisotopes; D011758:Pyrroles; D012414:Rubidium Radioisotopes; D019806:Cromakalim; D008914:Minoxidil; D000242:Cyclic AMP; D006152:Cyclic GMP; D003981:Diazoxide; D005905:Glyburide