The potassium channel opening drug cromakalim produces arterioselective vasodilation in the upper limbs of healthy volunteers.
1. The effect of the K+ channel opening drug cromakalim on forearm blood flow during direct infusion into the brachial artery, and on the size of noradrenaline preconstricted hand veins during infusion directly into the vein, was studied in eight healthy volunteers. 2. Cromakalim (0.01-10.0 micrograms min-1) produced a dose-dependent increase in blood flow in the infused forearm, from 5.4 +/- 2.5 to 15.1 +/- 7.3 ml 100 ml-1 forearm min-1 at 10 micrograms min-1 (P less than 0.001). The half-time of offset of its action was 30 min. There was no change in blood flow in the non-infused forearm. 3. There was no increase in the size of noradrenaline pre-constricted dorsal veins during local infusion of cromakalim (0.001-1.0 microgram min-1). Glyceryl trinitrate (0.4 microgram min-1) however, completely reversed the constriction to noradrenaline (P less than 0.001). 4. The clear arterioselectivity of cromakalim, as with other members of this new class of drug, accords with the dependency of venoconstriction on receptor-operated, rather than potential-operated mechanisms which are of importance in resistance vessels. With this haemodynamic profile cromakalim may prove of value in the treatment of arterial hypertension.
Department of Pharmacology and Clinical Pharmacology, St George's Hospital Medical School, London.
D J
DJ
Webb
N
N
Benjamin
P
P
Vallance
D000328:Adult; D001158:Arteries / Q000187:drug effects* / Q000502:physiology; D001578:Benzopyrans / Q000494:pharmacology*; D019806:Cromakalim; D005542:Forearm / Q000098:blood supply; D006225:Hand / Q000098:blood supply; D006801:Humans; D007261:Infusions, Intra-Arterial; D007262:Infusions, Intravenous; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D010276:Parasympatholytics / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects*; D011758:Pyrroles / Q000494:pharmacology*; D012039:Regional Blood Flow / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*
D001578:Benzopyrans; D010276:Parasympatholytics; D015221:Potassium Channels; D011758:Pyrroles; D019806:Cromakalim; D009638:Norepinephrine