Actions of co-dergocrine mesylate and its components at vascular smooth muscle.
The mechanisms by which co-dergocrine mesylate (CODE) and its components modify vascular tone was investigated in vitro. Changes in tension were monitored isometrically on spiral strips of canine basilar arteries and femoral veins suspended in 10 ml organ baths and on spiral strips of canine saphenous veins superfused between two platinum electrodes for electric stimulation (150 mA, 0.1 ms, 2 Hz) and measurement of tritium overflow. Cumulative concentration-response curves were established for 5-hydroxytryptamine (5-HT), noradrenaline (NA), dihydroergocornine (DHCO), dihydroergocristine (DHEC), dihydro-alpha-ergokryptine (DH alpha E), dihydro-beta-ergokryptine (DH beta E) and CODE. CODE and its single components were about equally potent in antagonizing responses to 5-HT on basilar arteries. On femoral veins DHEC antagonized responses to NA noncompetitively whereas the other components caused competitive antagonism against NA. Compared to CODE, DH alpha E and DH beta E, the alpha-blocking potency of both DHCO and DHEC was about 10 times weaker. All 5 ergot compounds were about equally potent in antagonizing contractile responses to electric stimulation of saphenous veins whereas the stimulation-induced overflow of labeled NA was inhibited in the following order of potency: CODE greater than or equal to DHCO greater than DH alpha E greater than DH beta E greater than DHEC. The 5 ergot compounds stimulated arterial and venous smooth muscle at slightly higher concentrations than necessary for antagonism of 5-HT or NA. Evidence is presented that the mechanism of the stimulant action on arteries differs from that on veins. It is suggested that the diversity of actions of CODE is the base for its therapeutic effectiveness in patients suffering from regional vascular disorders.
D000818:Animals; D001488:Basilar Artery / Q000187:drug effects; D004088:Dihydroergotoxine / Q000494:pharmacology*; D004285:Dogs; D004558:Electric Stimulation; D005260:Female; D005268:Femoral Vein / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology; D011985:Receptors, Serotonin / Q000187:drug effects; D012501:Saphenous Vein / Q000187:drug effects
D011985:Receptors, Serotonin; D004088:Dihydroergotoxine; D009638:Norepinephrine