Action of heparin and ruthenium red on responses of reversibly-permeabilised rat mesenteric arteries.
Heparin and ruthenium red were introduced intracellularly into rat mesenteric resistance arteries via reversible-permeabilisation. Heparin and ruthenium red inhibited contractile responses to noradrenaline, but not caffeine in Ca(2+)-free conditions. Neither heparin nor ruthenium red significantly inhibited peak contractile responses to K+, noradrenaline or caffeine in physiological saline, although heparin significantly increased the time taken for peak force to develop in response to noradrenaline. Noradrenaline and calcium concentration-response relationships were unaffected by heparin. Experiments with permeabilised, fura-2 loaded vessels indicated that heparin inhibited Ca2+ release induced by noradrenaline, but did not inhibit caffeine-induced Ca2+ release. The peak rise in intracellular Ca2+ following K+, or noradrenaline in physiological saline was unaffected by heparin. The use of reversible permeabilisation may prove a useful approach, allowing introduction of a variety of membrane-impermeant blockers of second messenger systems into intact resistance arteries.
Garcha
R S
RS
Department of Clinical Pharmacology, St. Mary's Hospital Medical School, Imperial College of Science, Technology & Medicine, London, UK.
Hughes
A D
AD
D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002463:Cell Membrane Permeability / Q000187:drug effects; D005453:Fluorescence; D006493:Heparin / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012430:Ruthenium Red / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects*
D012430:Ruthenium Red; D002110:Caffeine; D006493:Heparin; D002118:Calcium; D009638:Norepinephrine